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Molecular Profile	Treatment Approach
ABL1 rearrange	ABL Inhibitor (pan)

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
MLH1 negative	vaginal carcinoma	sensitive	Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab) is included in guidelines as preferred second-line or subsequent therapy for patients with recurrent or metastatic vaginal squamous cell carcinoma or adenocarcinoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
RET fusion	anaplastic thyroid carcinoma	sensitive	Selpercatinib	Guideline	Actionable	Retevmo (selpercatinib) is included in guidelines as neoadjuvant treatment for anaplastic thyroid carcinoma patients harboring RET fusions with stage IVa or IVb borderline resectable disease, and as a preferred systemic therapy for those with metastatic disease (NCCN.org).	detail...
IDH1 R132H	high grade glioma	not applicable	N/A	Guideline	Diagnostic	IDH1 R132H is diagnostic and aids in the diagnosis of gliomas (NCCN.org).	detail...
BRAF V600E	colon cancer	resistant	Cetuximab	Guideline	Actionable	Erbitux (cetuximab), as a monotherapy, is not indicated for use in colon cancer patients with BRAF V600E (NCCN.org).	detail...
IDH2 mutant	acute myeloid leukemia	sensitive	Decitabine + Venetoclax	Guideline	Actionable	Venclexta (venetoclax) in combination with Dacogen (decitabine) is included in guidelines for adult patients with acute myeloid leukemia harboring an IDH2 mutation (NCCN.org).	detail...
FGFR2 rearrange	extrahepatic bile duct carcinoma	sensitive	Futibatinib	Guideline	Actionable	Lytgobi (futibatinib) is included in guidelines as subsequent-line therapy (category 2A) for patients with cholangiocarcinoma harboring an FGFR2 fusion or rearrangement (NCCN.org).	detail...
MLH1 negative	ampulla of Vater adenocarcinoma	sensitive	Dostarlimab-gxly	Guideline	Actionable	Jemperli (dostarlimab-gxly) is included in guidelines as subsequent therapy for metastatic ampullary adenocarcinoma patients with deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
FGFR1 rearrange	myeloid and lymphoid neoplasms associated with FGFR1 abnormalities	sensitive	Midostaurin	Guideline	Actionable	Rydapt (midostaurin) is included in guidelines for patients with a myeloid/lymphoid neoplasm with eosinophilia harboring an FGFR1 rearrangement (NCCN.org).	detail...
FLT3 exon20	acute myeloid leukemia	sensitive	Cytarabine + Midostaurin	Guideline	Actionable	Rydapt (midostaurin) in combination with Cytosar-U (cytarabine) is included in guidelines as consolidation therapy for patients with acute myeloid leukemia harboring a mutation in the FLT3 tyrosine kinase domain (exons 14-23) (NCCN.org).	detail...
MLH1 negative	endometrial carcinoma	sensitive	Dostarlimab-gxly	Guideline	Actionable	Jemperli (dostarlimab-gxly) is included in guidelines as first-line or second-line therapy for patients with high microsatellite instability (MSI-H) or mismatch repair deficient (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) recurrent endometrial carcinoma (NCCN.org).	detail...
TP53 loss	chronic lymphocytic leukemia/small lymphocytic lymphoma	sensitive	Acalabrutinib + Obinutuzumab + Venetoclax	Guideline	Actionable	The combination of Venclexta (venetoclax), Gazyva (obinutuzumab), and Calquence (acalabrutinib) is included in guidelines as first-line therapy for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with TP53 loss (NCCN.org).	detail...
MLH1 negative	rectum cancer	sensitive	Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab) is included in guidelines as a preferred primary therapy for advanced or metastatic rectum cancer patients with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
TP53 mutant	chronic lymphocytic leukemia/small lymphocytic lymphoma	sensitive	Venetoclax	Guideline	Actionable	Venclexta (venetoclax) is included in guidelines as second-line or subsequent therapy for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with a TP53 mutation (NCCN.org).	detail...
MLH1 negative	rectum cancer	sensitive	Toripalimab-tpzi	Guideline	Actionable	Loqtorz (toripalimab-tpzi) is included in guidelines (category 2A) for patients with advanced or metastatic rectal cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
NTRK2 fusion	colon cancer	sensitive	Entrectinib	Guideline	Actionable	Rozlytrek (entrectinib) is included in guidelines for advanced or metastatic colon cancer patients with an NTRK fusion (NCCN.org).	detail...
TP53 mutant	essential thrombocythemia	not applicable	N/A	Guideline	Prognostic	TP53 mutations are associated with inferior leukemia-free survival in patients with essential thrombocythemia (NCCN.org).	detail...
PIK3CA exon10	colon cancer	sensitive	Aspirin	Guideline	Actionable	Aspirin is included in guidelines as adjuvant therapy (category 2A) for patients with advanced colon cancer harboring PIK3CA exon 10 (reported as exon 9) mutations, including hotspot mutations occurring at E542, E545, and Q546, and other somatic mutations affecting the PI3K pathway genes PIK3CA, PIK3R1, or PTEN (NCCN.org).	detail...
RET fusion	medullary thyroid carcinoma	sensitive	Pralsetinib	Guideline	Actionable	Gavreto (pralsetinib) is included in guidelines as a systemic therapy for patients with medullary thyroid carcinoma harboring pathogenic RET variants, including RET fusions (category 2B) (NCCN.org).	detail...
MLH1 negative	rectum cancer	sensitive	Penpulimab-kcqx	Guideline	Actionable	Penpulimab-kcqx (AK105) is included in guidelines (category 2A) for patients with advanced or metastatic rectal cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, MSH6, MSH2, or PMS2 expression by IHC) (NCCN.org).	detail...
MSH6 negative	small intestine adenocarcinoma	sensitive	Nivolumab	Guideline	Actionable	Opdivo (nivolumab) is included in guidelines as systemic therapy (category 2A) for patients with advanced or metastatic small bowel adenocarcinoma with deficient mismatch repair (dMMR, often defined by the loss of MSH6, MSH2, PMS2, or MLH1 expression by IHC) (NCCN.org).	detail...
FGFR2 fusion	cholangiocarcinoma	sensitive	Erdafitinib	Guideline	Actionable	Balversa (erdafitinib) is included in guidelines as subsequent-line therapy for patients with cholangiocarcinoma harboring FGFR2 fusions or rearrangements (NCCN.org).	detail...
PTEN inact mut	rectum cancer	sensitive	Aspirin	Guideline	Actionable	Aspirin is included in guidelines as adjuvant therapy (category 2A) for patients with advanced rectal cancer harboring inactivating PTEN mutations, including deep deletions, and other somatic mutations affecting the PI3K pathway genes PIK3CA or PIK3R1 (NCCN.org).	detail...
ATM inact mut	prostate cancer	sensitive	Enzalutamide + Talazoparib	Guideline	Actionable	Talzenna (talazoparib) plus Xtandi (enzalutamide) is included in guidelines as systemic therapy for patients with metastatic castration-resistant prostate cancer harboring a pathogenic germline or somatic ATM mutation who have not been treated in the setting of castration-resistant prostate cancer (NCCN.org).	detail...
MSH6 negative	esophagus adenocarcinoma	sensitive	Capecitabine + Nivolumab + Oxaliplatin	Guideline	Actionable	Opdivo (nivolumab), in combination with Xeloda (capecitabine) and Eloxatin (oxaliplatin) is included in guidelines as first-line therapy for patients with unresectable locally advanced, recurrent, or metastatic esophageal adenocarcinoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
MSH6 negative	esophagus squamous cell carcinoma	sensitive	Capecitabine + Oxaliplatin + Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab), in combination with Xeloda (capecitabine) and Eloxatin (oxaliplatin) is included in guidelines as first-line therapy for patients with unresectable locally advanced, recurrent, or metastatic esophagus squamous cell carcinoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
BRAF V600E	ganglioglioma	sensitive	Dabrafenib + Trametinib	Guideline	Actionable	Combination of Mekinist (trametinib) and Tafinlar (dabrafenib) is included in guidelines as an adjuvant treatment for patients with ganglioglioma harboring BRAF V600E (NCCN.org).	detail...
NTRK1 fusion	follicular thyroid carcinoma	sensitive	Larotrectinib	Guideline	Actionable	Vitrakvi (larotrectinib) is included in guidelines for patients with RAI-refractory oncocytic thyroid carcinoma harboring an NTRK fusion with progressive or symptomatic disease (NCCN.org).	detail...
NTRK2 fusion	ovary epithelial cancer	sensitive	Repotrectinib	Guideline	Actionable	Augtyro (repotrectinib) is included in guidelines as systemic therapy for patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer harboring an NTRK fusion (NCCN.org).	detail...
IDH1 act mut	astrocytoma, IDH-mutant, grade 3	sensitive	Vorasidenib	Guideline	Actionable	Voranigo (vorasidenib) is included in guidelines for patients with recurrent or progressive (category 2B) WHO grade 3 astrocytoma harboring an IDH1 activating mutation or as adjuvant treatment (category 2B) (NCCN.org).	detail...
NTRK1 fusion	ampulla of Vater adenocarcinoma	sensitive	Entrectinib	Guideline	Actionable	Rozlytrek (entrectinib) is included in guidelines as first-line or subsequent therapy for patients with metastatic ampullary adenocarcinoma harboring NTRK fusions (NCCN.org).	detail...
FLT3 exon 14 ins	acute myeloid leukemia	sensitive	Midostaurin	Guideline	Actionable	Rydapt (midostaurin) is included in guidelines as maintenance therapy for patients with acute myeloid leukemia harboring a FLT3 internal tandem duplication (FLT3-ITD) mutation (NCCN.org).	detail...
MLH1 negative	Adenocarcinoma of Unknown Primary	sensitive	Dostarlimab-gxly	Guideline	Actionable	Jemperli (dostarlimab-gxly) is included in guidelines for patients with adenocarcinoma of unknown primary with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
IDH1 mutant	myelodysplastic syndrome	sensitive	Ivosidenib	Guideline	Actionable	Tibsovo (ivosidenib) is included in guidelines for patients with lower-risk (category 2A) or higher-risk (category 2B) relapsed or refractory myelodysplastic syndrome harboring an IDH1 mutation (NCCN.org).	detail...
MLH1 negative	colon cancer	sensitive	Retifanlimab	Guideline	Actionable	Zynyz (retifanlimab) is included in guidelines (category 2A) for patients with advanced or metastatic colon cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, MSH2, PMS2, or MSH6 expression by IHC) (NCCN.org).	detail...
NTRK2 fusion	glioblastoma	sensitive	Repotrectinib	Guideline	Actionable	Augtyro (repotrectinib) is included in guidelines (category 2B) for patients with recurrent glioblastoma harboring an NTRK fusion (NCCN.org).	detail...
BRAF V600E	pilocytic astrocytoma	sensitive	Selumetinib	Guideline	Actionable	Koselugo (selumetinib) is included in guidelines for patients with recurrent or progressive pilocytic astrocytoma harboring BRAF V600E (NCCN.org).	detail...
MSH6 negative	esophagus adenocarcinoma	sensitive	Dostarlimab-gxly	Guideline	Actionable	Jemperli (dostarlimab-gxly) is included in guidelines as neoadjuvant, preferred first-line, second-line, or subsequent therapy for patients with unresectable locally advanced, recurrent, or metastatic esophageal adenocarcinoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
FLT3 exon14	acute myeloid leukemia	sensitive	Cytarabine + Daunorubicin + Midostaurin	Guideline	Actionable	Rydapt (midostaurin), in combination with Cerubidine (daunorubicin) and Cytosar-U (cytarabine), is included in guidelines for patients with acute myeloid leukemia harboring a mutation in the FLT3 tyrosine kinase domain (exons 14-23) (NCCN.org).	detail...
MSH6 negative	small intestine adenocarcinoma	sensitive	Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab) is included in guidelines as systemic therapy (category 2A) for patients with advanced or metastatic small bowel adenocarcinoma with deficient mismatch repair (dMMR, often defined by the loss of MSH6, MSH2, PMS2, or MLH1 expression by IHC) (NCCN.org).	detail...
TP53 loss	chronic lymphocytic leukemia/small lymphocytic lymphoma	sensitive	Ibrutinib + Lisocabtagene maraleucel	Guideline	Actionable	Breyanzi (lisocabtagene maraleucel) in combination with Imbruvica (ibrutinib) is included in guidelines for patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma with TP53 loss after prior BTK inhibitor-based and BCL2 inhibitor-containing regimens (NCCN.org).	detail...
NTRK2 fusion	vaginal carcinoma	sensitive	Entrectinib	Guideline	Actionable	Rozlytrek (entrectinib) is included in guidelines as second-line or subsequent therapy for patients with recurrent or metastatic vaginal squamous cell carcinoma or adenocarcinoma harboring an NTRK fusion (NCCN.org).	detail...
IDH2 mutant	angioimmunoblastic T-cell lymphoma	not applicable	N/A	Guideline	Diagnostic	IDH2 mutations aid in the diagnosis of angioimmunoblastic T-cell lymphoma (NCCN.org).	detail...
BRAF V600E	gastrointestinal stromal tumor	sensitive	Dabrafenib + Trametinib	Guideline	Actionable	Tafinlar (dabrafenib) in combination with Mekinist (trametinib) is included in guidelines as neoadjuvant therapy for patients with resectable disease and as first-line systemic therapy for patients with unresectable or metastatic gastrointestinal stromal tumor (GIST) harboring BRAF V600E (NCCN.org).	detail...
BRAF V600K	skin melanoma	sensitive	Dabrafenib + Trametinib	Guideline	Actionable	Tafinlar (dabrafenib) and Mekinist (trametinib) combination therapy is included in guidelines for melanoma patients harboring a BRAF V600 mutation, such as BRAF V600K, as neoadjuvant or adjuvant therapy for stage III disease and as systemic therapy for patients with unresectable or metastatic disease (NCCN.org).	detail...
FLT3 exon 14 ins	myelodysplastic syndrome	not applicable	N/A	Guideline	Prognostic	FLT3 internal tandem duplication (FLT3-ITD) mutations are associated with poor prognosis in patients with myelodysplastic syndrome (NCCN.org).	detail...
BRAF V600E	colon cancer	sensitive	Encorafenib + Panitumumab	Guideline	Actionable	Braftovi (encorafenib) in combination with Vectibix (panitumumab) is included in guidelines (category 2A) as primary or subsequent therapy for patients with colon cancer harboring BRAF V600E (NCCN.org).	detail...
BRAF V600E	lung non-small cell carcinoma	sensitive	Dabrafenib	Guideline	Actionable	Tafinlar (dabrafenib) is in guidelines as a first-line therapy for patients with advanced or metastatic non-small cell lung cancer with BRAF V600E mutations who can not tolerate the combination of Mekinist (trametinib) and Tafinlar (dabrafenib) (NCCN.org).	detail...
NTRK1 fusion	extrahepatic bile duct carcinoma	sensitive	Repotrectinib	Guideline	Actionable	Augtyro (repotrectinib) is included in guidelines as primary and subsequent-line therapy (category 2A) for patients with unresectable or metastatic biliary tract cancer harboring NTRK fusions, including extrahepatic cholangiocarcinoma (NCCN.org).	detail...
BRAF V600E	neuroendocrine tumor	sensitive	Dabrafenib + Trametinib	Guideline	Actionable	Mekinist (trametinib) and Tafinlar (dabrafenib) combination therapy is included in guidelines for patients with unresectable or metastatic extrapulmonary poorly differentiated neuroendocrine carcinoma, large or small cell carcinoma, or mixed neuroendocrine/non-neuroendocrine neoplasms harboring BRAF V600E who have progressed on or following prior treatment (NCCN.org).	detail...
RET fusion	breast cancer	sensitive	Selpercatinib	Guideline	Actionable	Retevmo (selpercatinib) is included in guidelines for patients with recurrent unresectable or stage IV (M1) breast cancer harboring RET fusions (NCCN.org).	detail...
NTRK2 fusion	extrahepatic bile duct carcinoma	sensitive	Larotrectinib	Guideline	Actionable	Vitrakvi (larotrectinib) is included in guidelines as primary and subsequent-line therapy for patients with unresectable or metastatic biliary tract cancer harboring an NTRK fusion, including extrahepatic cholangiocarcinoma (NCCN.org).	detail...
MSH6 negative	chordoma	sensitive	Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab) is included in guidelines as systemic therapy for metastatic chordoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
NTRK2 fusion	hepatocellular carcinoma	sensitive	Repotrectinib	Guideline	Actionable	Augtyro (repotrectinib) is included in guidelines for patients with hepatocellular carcinoma harboring an NTRK fusion (NCCN.org).	detail...
BRAF V600E	skin melanoma	sensitive	Dabrafenib + Trametinib	Guideline	Actionable	Tafinlar (dabrafenib) and Mekinist (trametinib) combination therapy is included in guidelines for cutaneous melanoma patients harboring a BRAF V600 mutation, such as BRAF V600E, as neoadjuvant or adjuvant therapy for stage III disease and as systemic therapy for patients with unresectable or metastatic disease (NCCN.org).	detail...
TP53 loss	chronic lymphocytic leukemia/small lymphocytic lymphoma	sensitive	Pirtobrutinib	Guideline	Actionable	Jaypirca (pirtobrutinib) is included in guidelines (category 1) as second-line or subsequent therapy for patients with chronic lymphocytic leukemia/small lymphocytic lymphoma with TP53 loss and for patients with relapsed or refractory disease after prior BTK inhibitor and BCL2 inhibitor-containing therapy (NCCN.org).	detail...
NTRK1 fusion	extrahepatic bile duct carcinoma	sensitive	Entrectinib	Guideline	Actionable	Rozlytrek (entrectinib) is included in guidelines as primary and subsequent-line therapy for patients with unresectable or metastatic biliary tract cancer harboring an NTRK fusion, including extrahepatic cholangiocarcinoma (NCCN.org).	detail...
MLH1 negative	oral cavity cancer	sensitive	Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab) is included in guidelines as first- and subsequent-line therapy for patients with mismatch repair deficient (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) recurrent, unresectable, or metastatic oral cavity cancer (NCCN.org).	detail...
TP53 mutant	chronic lymphocytic leukemia/small lymphocytic lymphoma	sensitive	Lenalidomide + Rituximab	Guideline	Actionable	Revlimid (lenalidomide) combined with Rituxan (rituximab) is included in guidelines for patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma with a TP53 mutation after prior BTK inhibitor-based and BCL2 inhibitor-containing regimens (NCCN.org).	detail...
NTRK1 fusion	skin melanoma	sensitive	Larotrectinib	Guideline	Actionable	Vitrakvi (larotrectinib) therapy is included in guidelines for patients with metastatic or unresectable cutaneous melanoma harboring an NTRK fusion (NCCN.org).	detail...
MLH1 negative	rectum cancer	sensitive	Avelumab	Guideline	Actionable	Bavencio (avelumab) is included in guidelines (category 2A) for patients with advanced or metastatic rectal cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, MSH2, MSH6, or PMS2 expression by IHC) (NCCN.org).	detail...
NTRK2 fusion	esophagus adenocarcinoma	sensitive	Repotrectinib	Guideline	Actionable	Augtyro (repotrectinib) is included in guidelines as second-line or subsequent therapy for patients with unresectable locally advanced, recurrent, or metastatic esophageal adenocarcinoma with an NTRK fusion (NCCN.org).	detail...
MSH6 negative	esophagus squamous cell carcinoma	sensitive	Ipilimumab + Nivolumab	Guideline	Actionable	Opdivo (nivolumab), in combination with Yervoy (ipilimumab), is included in guidelines as first-line, second-line, or subsequent therapy for patients with unresectable locally advanced, recurrent, or metastatic esophagus squamous cell carcinoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
FLT3 exon17	acute myeloid leukemia	sensitive	Cytarabine + Idarubicin + Midostaurin	Guideline	Actionable	Rydapt (midostaurin) in combination with Idamycin (idarubicin) and Cytosar-U (cytarabine) is included in guidelines for patients with acute myeloid leukemia harboring a mutation in the FLT3 tyrosine kinase domain (exons 14-23) (NCCN.org).	detail...
NTRK2 fusion	extrahepatic bile duct carcinoma	sensitive	Entrectinib	Guideline	Actionable	Rozlytrek (entrectinib) is included in guidelines as primary and subsequent-line therapy for patients with unresectable or metastatic biliary tract cancer harboring an NTRK fusion, including extrahepatic cholangiocarcinoma (NCCN.org).	detail...
BRAF V600E	Erdheim-Chester disease	sensitive	Dabrafenib	Guideline	Actionable	Tafinlar (dabrafenib) is included in guidelines as first-line or subsequent-line therapy for patients with Erdheim-Chester disease harboring BRAF V600E (NCCN.org).	detail...
NTRK2 fusion	appendix adenocarcinoma	sensitive	Repotrectinib	Guideline	Actionable	Augtyro (repotrectinib) is included in guidelines (category 2A) as second-line or subsequent therapy for patients with advanced or metastatic appendiceal adenocarcinoma harboring an NTRK fusion (NCCN.org).	detail...
NTRK2 fusion	oncocytic carcinoma of the thyroid	sensitive	Entrectinib	Guideline	Actionable	Rozlytrek (entrectinib) is included in guidelines for patients with RAI-refractory oncocytic thyroid carcinoma harboring an NTRK fusion with progressive or symptomatic disease (NCCN.org).	detail...
FLT3 exon14	acute myeloid leukemia	sensitive	Gilteritinib	Guideline	Actionable	Xospata (gilteritinib) is included in guidelines for patients with relapsed or refractory acute myeloid leukemia harboring a mutation in the FLT3 tyrosine kinase domain (exons 14-23) (NCCN.org).	detail...
NTRK1 fusion	Adenocarcinoma of Unknown Primary	sensitive	Repotrectinib	Guideline	Actionable	Augtyro (repotrectinib) is included in guidelines for patients with adenocarcinoma of unknown primary harboring NTRK1 fusions (NCCN.org).	detail...
CDKN2A mutant	skin melanoma	not applicable	N/A	Guideline	Risk Factor	Germline CDKN2A mutations or polymorphisms are associated with increased risk of developing single or multiple primary cutaneous melanomas (NCCN.org).	detail...
FGFR2 fusion	salivary gland cancer	sensitive	Erdafitinib	Guideline	Actionable	Balversa (erdafitinib) is included in guidelines for patients with unresectable locally advanced, recurrent, or metastatic salivary gland tumors harboring FGFR mutations or fusions (category 2B) who received prior systemic therapy and have no alternative systemic therapy available (NCCN.org).	detail...
NTRK1 fusion	stomach cancer	sensitive	Larotrectinib	Guideline	Actionable	Vitrakvi (larotrectinib) is included in guidelines as second-line or subsequent therapy for patients with unresectable locally advanced, recurrent, or metastatic gastric cancer harboring an NTRK fusion (NCCN.org).	detail...
MLH1 negative	ampulla of Vater adenocarcinoma	sensitive	Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab) is included in guidelines as first-line or subsequent therapy for metastatic ampullary adenocarcinoma patients with deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
TP53 mutant	chronic lymphocytic leukemia/small lymphocytic lymphoma	sensitive	Pirtobrutinib	Guideline	Actionable	Jaypirca (pirtobrutinib) is included in guidelines (category 1) as second-line or subsequent therapy for patients with chronic lymphocytic leukemia/small lymphocytic lymphoma with a TP53 mutation and for patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma with a TP53 mutation after prior BTK inhibitor-based and BCL2 inhibitor-containing regimens (NCCN.org).	detail...
NRAS exon2	colon cancer	resistant	Cetuximab	Guideline	Actionable	Erbitux (cetuximab) is not indicated for use in colon cancer patients with NRAS exon 2 mutations (NCCN.org).	detail...
BRAF V600X	skin melanoma	sensitive	Atezolizumab + Cobimetinib + Vemurafenib	Guideline	Actionable	Zelboraf (vemurafenib) plus Cotellic (cobimetinib) in combination with an immune checkpoint inhibitor, such as Tecentriq (atezolizumab), is included in guidelines as second-line or subsequent therapy (category 2A) for patients with metastatic or unresectable cutaneous melanoma harboring a BRAF V600 mutation (NCCN.org).	detail...
BRAF V600K	skin melanoma	sensitive	Binimetinib + Encorafenib	Guideline	Actionable	Braftovi (encorafenib) in combination with Mektovi (binimetinib) is included in guidelines as first-line and second-line therapy for patients with metastatic or unresectable cutaneous melanoma harboring BRAF V600E or V600K mutations (PMID: 30959471; NCCN.org).	30959471 detail...
FGFR3 act mut	glottis cancer	sensitive	Erdafitinib	Guideline	Actionable	Balversa (erdafitinib) is included in guidelines as subsequent-line therapy (category 2B) for patients with glottic larynx cancer harboring FGFR mutations or fusions and with no alternative options (NCCN.org).	detail...
FLT3 exon17	acute myeloid leukemia	sensitive	Gilteritinib	Guideline	Actionable	Xospata (gilteritinib) is included in guidelines for patients with relapsed or refractory acute myeloid leukemia harboring a mutation in the FLT3 tyrosine kinase domain (exons 14-23) (NCCN.org).	detail...
NRAS exon3	rectum cancer	resistant	Panitumumab	Guideline	Actionable	Vectibix (panitumumab) is not indicated for use in rectum cancer patients with NRAS exon 3 mutations (NCCN.org).	detail...
BRAF V600E	small intestine adenocarcinoma	sensitive	Cetuximab + Encorafenib + Fluorouracil + Leucovorin + Oxaliplatin	Guideline	Actionable	Braftovi (encorafenib) in combination with Erbitux (cetuximab) and FOLFOX is included in guidelines as initial or subsequent-line therapy (category 2A) therapy for patients with advanced or metastatic small bowel adenocarcinoma harboring BRAF V600E (NCCN.org).	detail...
BRAF V600E	appendix adenocarcinoma	sensitive	Cetuximab + Encorafenib	Guideline	Actionable	Braftovi (encorafenib) in combination with Erbitux (cetuximab) is included in guidelines (category 2A) for patients with advanced or metastatic appendiceal adenocarcinoma harboring BRAF V600E (NCCN.org).	detail...
IDH1 mutant	cholangiocarcinoma	sensitive	Ivosidenib	Guideline	Actionable	Tibsovo (ivosidenib) is included in guidelines as subsequent therapy (category 1) for cholangiocarcinoma patients harboring IDH1 mutations (NCCN.org).	detail...
MSH6 negative	intrahepatic cholangiocarcinoma	sensitive	Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab) is included in guidelines as primary therapy and subsequent-line therapy for patients with unresectable or metastatic biliary tract cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC), including intrahepatic cholangiocarcinoma (NCCN.org).	detail...
NTRK2 fusion	Adenocarcinoma of Unknown Primary	sensitive	Larotrectinib	Guideline	Actionable	Vitrakvi (larotrectinib) is included in guidelines for patients with adenocarcinoma of unknown primary harboring NTRK2 fusions (NCCN.org).	detail...
BRAF V600X	pilocytic astrocytoma	sensitive	Tovorafenib	Guideline	Actionable	Ojemda (tovorafenib) is included in guidelines (category 2A) for patients with recurrent or progressive circumscribed glioma, including pilocytic astrocytoma, harboring BRAF fusions, rearrangements, or BRAF V600 mutations (NCCN.org).	detail...
MLH1 negative	stomach cancer	sensitive	Fluorouracil + Nivolumab + Oxaliplatin	Guideline	Actionable	Opdivo (nivolumab), in combination with Adrucil (fluorouracil) and Eloxatin (oxaliplatin) is included in guidelines as first-line therapy for patients with unresectable locally advanced, recurrent, or metastatic gastric cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
NTRK2 fusion	gallbladder cancer	sensitive	Repotrectinib	Guideline	Actionable	Augtyro (repotrectinib) is included in guidelines as primary and subsequent-line therapy (category 2A) for patients with unresectable or metastatic biliary tract cancer harboring NTRK fusions, including gallbladder cancer (NCCN.org)	detail...
RET rearrange	lung non-small cell carcinoma	sensitive	Cabozantinib	Guideline	Actionable	Cometriq (cabozantinib) is in guidelines as subsequent therapy for patients with advanced or metastatic non-small cell lung cancer harboring RET rearrangements (NCCN.org).	detail...
FLT3 exon 14 ins	acute myeloid leukemia	not applicable	N/A	Guideline	Prognostic	FLT3 internal tandem duplication (FLT3-ITD) mutations are associated with inferior prognosis in acute myeloid leukemia patients with normal karyotype (NCCN.org).	detail...
NTRK2 fusion	soft tissue sarcoma	sensitive	Repotrectinib	Guideline	Actionable	Augtyro (repotrectinib) is included in guidelines as a preferred first-line or subsequent therapy for patients with soft tissue sarcoma harboring an NTRK2 fusion (NCCN.org).	detail...
PIK3CA exon21	rectum cancer	sensitive	Aspirin	Guideline	Actionable	Aspirin is included in guidelines as adjuvant therapy (category 2A) for patients with advanced rectal cancer harboring PIK3CA exon 21 (reported as exon 20) mutations, including hotspot mutations occurring at Y1021, M1043, N1044, and H1047, and other somatic mutations affecting the PI3K pathway genes PIK3CA, PIK3R1, or PTEN (NCCN.org).	detail...
MSH6 negative	small intestine adenocarcinoma	sensitive	Durvalumab	Guideline	Actionable	Imfinzi (durvalumab) is included in guidelines as systemic therapy (category 2A) for patients with advanced or metastatic small bowel adenocarcinoma with deficient mismatch repair (dMMR, often defined by the loss of MSH6, MSH2, PMS2, or MLH1 expression by IHC) (NCCN.org).	detail...
NTRK1 fusion	stomach cancer	sensitive	Entrectinib	Guideline	Actionable	Rozlytrek (entrectinib) is included in guidelines as second-line or subsequent therapy for patients with unresectable locally advanced, recurrent, or metastatic gastric cancer harboring an NTRK fusion (NCCN.org).	detail...
JAK2 rearrange	myeloid neoplasm	sensitive	Fedratinib	Guideline	Actionable	Inrebic (fedratinib) is included in guidelines for patients with a myeloid/lymphoid neoplasm with eosinophilia harboring a JAK2 rearrangement (NCCN.org).	detail...
MLH1 negative	appendix adenocarcinoma	sensitive	Penpulimab-kcqx	Guideline	Actionable	Penpulimab-kcqx (AK105) is included in guidelines (category 2A) for patients with advanced or metastatic appendiceal adenocarcinoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
PDGFRB rearrange	B-cell acute lymphoblastic leukemia	not applicable	N/A	Guideline	Prognostic	PDGFRB rearrangements are associated with a poor prognosis in patients with B-cell acute lymphoblastic leukemia (NCCN.org).	detail...
FGFR1 fusion	oral cavity cancer	sensitive	Erdafitinib	Guideline	Actionable	Balversa (erdafitinib) is included in guidelines as subsequent-line therapy (category 2B) for patients with oral cavity cancer harboring FGFR mutations or fusions and with no alternative options (NCCN.org).	detail...
MLH1 mutant	stomach cancer	not applicable	N/A	Guideline	Risk Factor	Germline mutations in MLH1 result in Lynch syndrome, which is associated with increased risk of early onset of gastric cancer (NCCN.org).	detail...
NTRK1 fusion	appendix adenocarcinoma	sensitive	Repotrectinib	Guideline	Actionable	Augtyro (repotrectinib) is included in guidelines (category 2A) as second-line or subsequent therapy for patients with advanced or metastatic appendiceal adenocarcinoma harboring an NTRK fusion (NCCN.org).	detail...
NTRK2 fusion	Squamous Cell Carcinoma of Unknown Primary	sensitive	Repotrectinib	Guideline	Actionable	Augtyro (repotrectinib) is included in guidelines for patients with squamous cell carcinoma of unknown primary harboring NTRK2 fusions (NCCN.org).	detail...
NTRK2 fusion	gastrointestinal stromal tumor	sensitive	Larotrectinib	Guideline	Actionable	Vitrakvi (larotrectinib) is included in guidelines as neoadjuvant therapy for patients with resectable disease and as first-line systemic therapy for patients with unresectable or metastatic gastrointestinal stromal tumor (GIST) harboring NTRK fusions (NCCN.org).	detail...
RET fusion	uterine corpus sarcoma	sensitive	Selpercatinib	Guideline	Actionable	Retevmo (selpercatinib) is included in guidelines as first-line therapy for patients with advanced, recurrent/metastatic, or inoperable uterine sarcomas harboring RET fusions (NCCN.org).	detail...
NTRK2 fusion	esophagus squamous cell carcinoma	sensitive	Larotrectinib	Guideline	Actionable	Vitrakvi (larotrectinib) is included in guidelines as second-line or subsequent therapy for patients with unresectable locally advanced, recurrent, or metastatic esophageal squamous cell carcinoma with an NTRK fusion (NCCN.org).	detail...
MLH1 negative	maxillary sinus cancer	sensitive	Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab) is included in guidelines as first- and subsequent-line therapy for patients with mismatch repair deficient (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) recurrent, unresectable, or metastatic maxillary sinus cancer (NCCN.org).	detail...
TP53 mutant	skin melanoma	not applicable	N/A	Guideline	Risk Factor	Germline TP53 mutations or polymorphisms are associated with increased risk of developing single or multiple primary cutaneous melanomas (NCCN.org).	detail...
ALK fusion	Erdheim-Chester disease	sensitive	Crizotinib	Guideline	Actionable	Xalkori (crizotinib) is included in guidelines as first-line or subsequent-line therapy for patients with Erdheim-Chester disease harboring ALK fusions (NCCN.org).	detail...
FGFR1 act mut	oropharynx cancer	sensitive	Erdafitinib	Guideline	Actionable	Balversa (erdafitinib) is included in guidelines as subsequent-line therapy (category 2B) for patients with oropharynx cancer harboring FGFR mutations or fusions and with no alternative options (NCCN.org).	detail...
FGFR2 act mut	maxillary sinus cancer	sensitive	Erdafitinib	Guideline	Actionable	Balversa (erdafitinib) is included in guidelines as subsequent-line therapy (category 2B) for patients with maxillary sinus cancer harboring FGFR mutations or fusions and with no alternative options (NCCN.org).	detail...
CBL mutant	systemic mastocytosis	not applicable	N/A	Guideline	Prognostic	CBL mutations are associated with an adverse prognosis in patients with systemic mastocytosis (NCCN.org).	detail...
NRAS exon3	colon cancer	resistant	Cetuximab	Guideline	Actionable	Erbitux (cetuximab) is not indicated for use in colon cancer patients with NRAS exon 3 mutations (NCCN.org).	detail...
NTRK2 fusion	endometrial carcinoma	sensitive	Repotrectinib	Guideline	Actionable	Augtyro (repotrectinib) is included in guidelines as a second-line or subsequent-line therapy for patients with recurrent endometrial carcinoma harboring an NTRK fusion (NCCN.org).	detail...
NTRK1 fusion	papillary thyroid carcinoma	sensitive	Entrectinib	Guideline	Actionable	Rozlytrek (entrectinib) is included in guidelines for patients with RAI-refractory papillary thyroid carcinoma harboring an NTRK fusion with progressive or symptomatic disease (NCCN.org).	detail...
ALK rearrange ALK G1202R	lung non-small cell carcinoma	sensitive	Lorlatinib	Guideline	Actionable	Lorbrena (lorlatinib) is included in guidelines as subsequent therapy for patients with advanced or metastatic ALK-rearranged non-small cell lung cancer harboring ALK G1202R (NCCN.org).	detail...
KIT act mut	skin melanoma	sensitive	Ripretinib	Guideline	Actionable	Qinlock (ripretinib) is included in guidelines as second-line therapy for metastatic or unresectable cutaneous melanoma patients with KIT activating mutations (NCCN.org).	detail...
RET fusion	follicular thyroid carcinoma	sensitive	Selpercatinib	Guideline	Actionable	Retevmo (selpercatinib) is included in guidelines for patients with RAI-refractory follicular thyroid carcinoma harboring a RET fusion with progressive or symptomatic disease (NCCN.org).	detail...
IDH2 mutant	essential thrombocythemia	not applicable	N/A	Guideline	Prognostic	The presence of at least one mutation in either SH2B3, IDH2, U2AF1, SRSF2, SF3B1, EZH2, TP53, or RUNX1 is associated with inferior overall survival in patients with essential thrombocythemia (NCCN.org).	detail...
TP53 mutant	chronic lymphocytic leukemia/small lymphocytic lymphoma	sensitive	Venetoclax + Zanubrutinib	Guideline	Actionable	Venclexta (venetoclax) combined with Brukinsa (zanubrutinib) is included in guidelines as first-line therapy for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with a TP53 mutation (NCCN.org).	detail...
NTRK2 fusion	glioblastoma	sensitive	Larotrectinib	Guideline	Actionable	Vitrakvi (larotrectinib) is included in guidelines for patients with recurrent glioblastoma harboring an NTRK fusion (NCCN.org).	detail...
IDH2 mutant	acute myeloid leukemia	sensitive	Azacitidine	Guideline	Actionable	Vidaza (azacitidine) is included in guidelines for adult patients with acute myeloid leukemia harboring an IDH2 mutation (NCCN.org).	detail...
IDH2 mutant	myelofibrosis	not applicable	N/A	Guideline	Prognostic	IDH2 mutations are associated with inferior leukemia-free survival in patients with myelofibrosis (NCCN.org).	detail...
MAP2K1 mutant	follicular lymphoma	not applicable	N/A	Guideline	Diagnostic	MAP2K1 mutations aid in the diagnosis of follicular lymphoma (NCCN.org).	detail...
MSH6 negative	Squamous Cell Carcinoma of Unknown Primary	sensitive	Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab) is included in guidelines for patients with squamous cell carcinoma of unknown primary with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
MLH1 negative	rectum cancer	sensitive	Ipilimumab + Nivolumab	Guideline	Actionable	Opdivo (nivolumab) in combination with Yervoy (ipilimumab) is included in guidelines as a primary therapy for advanced or metastatic rectum cancer patients with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
MLH1 negative	Ewing sarcoma	sensitive	Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab) is included in guidelines as systemic therapy for metastatic Ewing sarcoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
NTRK1 fusion	ovary epithelial cancer	sensitive	Entrectinib	Guideline	Actionable	Rozlytrek (entrectinib) is included in guidelines as systemic therapy for patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer harboring an NTRK fusion (NCCN.org).	detail...
BRAF rearrange	pleomorphic xanthoastrocytoma	sensitive	Tovorafenib	Guideline	Actionable	Ojemda (tovorafenib) is included in guidelines (category 2A) for patients with recurrent or progressive circumscribed glioma, including pleomorphic xanthoastrocytoma, harboring BRAF fusions, rearrangements, or BRAF V600 mutations (NCCN.org).	detail...
FLT3 exon 15 ins	acute myeloid leukemia	sensitive	Cytarabine + Idarubicin + Midostaurin	Guideline	Actionable	Rydapt (midostaurin) in combination with Idamycin (idarubicin) and Cytosar-U (cytarabine) is included in guidelines for patients with acute myeloid leukemia harboring a FLT3 internal tandem duplication (FLT3-ITD) mutation (NCCN.org).	detail...
MSH6 negative	appendix adenocarcinoma	sensitive	Toripalimab-tpzi	Guideline	Actionable	Loqtorz (toripalimab-tpzi) is included in guidelines (category 2A) for patients with advanced or metastatic appendiceal adenocarcinoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
BRAF V600E	gallbladder cancer	sensitive	Dabrafenib + Trametinib	Guideline	Actionable	Tafinlar (dabrafenib) in combination with Mekinist (trametinib) is included in guidelines as subsequent-line therapy for patients with biliary cancer harboring BRAF V600E, including gallbladder cancer (NCCN.org).	detail...
FLT3 exon14	acute myeloid leukemia	sensitive	Cytarabine + Idarubicin + Midostaurin	Guideline	Actionable	Rydapt (midostaurin) in combination with Idamycin (idarubicin) and Cytosar-U (cytarabine) is included in guidelines for patients with acute myeloid leukemia harboring a mutation in the FLT3 tyrosine kinase domain (exons 14-23) (NCCN.org).	detail...
IDH2 act mut	astrocytoma, IDH-mutant, grade 3	sensitive	Vorasidenib	Guideline	Actionable	Voranigo (vorasidenib) is included in guidelines for patients with recurrent or progressive (category 2B) WHO grade 3 astrocytoma harboring an IDH2 activating mutation or as adjuvant treatment (category 2B) (NCCN.org).	detail...
FLT3 exon15	acute myeloid leukemia	sensitive	Cytarabine + Idarubicin + Midostaurin	Guideline	Actionable	Rydapt (midostaurin) in combination with Idamycin (idarubicin) and Cytosar-U (cytarabine) is included in guidelines for patients with acute myeloid leukemia harboring a mutation in the FLT3 tyrosine kinase domain (exons 14-23) (NCCN.org).	detail...
NTRK1 fusion	breast cancer	sensitive	Entrectinib	Guideline	Actionable	Rozlytrek (entrectinib) therapy is included in guidelines for patients with recurrent unresectable or stage IV (M1) breast cancer harboring an NTRK fusion (NCCN.org).	detail...
MLH1 negative	gastroesophageal junction adenocarcinoma	sensitive	Fluorouracil + Oxaliplatin + Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab), in combination with Adrucil (fluorouracil) and Eloxatin (oxaliplatin) is included in guidelines as first-line therapy for patients with unresectable locally advanced, recurrent, or metastatic gastroesophageal junction adenocarcinoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
KMT2A rearrange	acute myeloid leukemia	sensitive	Revumenib	Guideline	Actionable	Revuforj (revumenib) is included in guidelines for patients with relapsed or refractory acute myeloid leukemia harboring a KMT2A rearrangement (NCCN.org).	detail...
MSH6 negative	appendix adenocarcinoma	sensitive	Penpulimab-kcqx	Guideline	Actionable	Penpulimab-kcqx (AK105) is included in guidelines (category 2A) for patients with advanced or metastatic appendiceal adenocarcinoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
KIT act mut	skin melanoma	sensitive	Dasatinib	Guideline	Actionable	Sprycel (dasatinib) is included in guidelines as second-line therapy for metastatic or unresectable cutaneous melanoma patients with KIT activating mutations (NCCN.org).	detail...
MSH6 negative	appendix adenocarcinoma	sensitive	Dostarlimab-gxly	Guideline	Actionable	Jemperli (dostarlimab-gxly) is included in guidelines (category 2A) for patients with advanced or metastatic appendiceal adenocarcinoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
MLH1 negative	gastroesophageal junction adenocarcinoma	sensitive	Capecitabine + Nivolumab + Oxaliplatin	Guideline	Actionable	Opdivo (nivolumab), in combination with Xeloda (capecitabine) and Eloxatin (oxaliplatin) is included in guidelines as first-line therapy for patients with unresectable locally advanced, recurrent, or metastatic gastroesophageal junction adenocarcinoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
MLH1 negative	chondrosarcoma	sensitive	Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab) is included in guidelines as systemic therapy for metastatic chondrosarcoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
CSF1R mutant	Erdheim-Chester disease	sensitive	Pexidartinib	Guideline	Actionable	Turalio (pexidartinib) is included in guidelines as first-line or subsequent-line therapy for patients with Erdheim-Chester disease harboring CSF1R mutations (NCCN.org).	detail...
NTRK1 fusion	breast cancer	sensitive	Larotrectinib	Guideline	Actionable	Vitrakvi (larotrectinib) therapy is included in guidelines for patients with recurrent unresectable or stage IV (M1) breast cancer harboring an NTRK fusion (NCCN.org).	detail...
RET A883X	medullary thyroid carcinoma	not applicable	N/A	Guideline	Risk Factor	Germline RET A883X mutations result in multiple endocrine neoplasia, type 2B (MEN 2B), which is associated with high risk of developing medullary thyroid carcinoma (NCCN.org).	detail...
MLH1 negative	ethmoid sinus cancer	sensitive	Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab) is included in guidelines as first- and subsequent-line therapy for patients with mismatch repair deficient (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) recurrent, unresectable, or metastatic ethmoid sinus cancer (NCCN.org).	detail...
NTRK1 fusion	vulva squamous cell carcinoma	sensitive	Larotrectinib	Guideline	Actionable	Vitrakvi (larotrectinib) is included in guidelines as a second-line or subsequent therapy for patients with advanced or recurrent/metastatic vulvar squamous cell carcinoma harboring an NTRK fusion (NCCN.org).	detail...
NRAS wild-type	colon cancer	predicted - sensitive	Cetuximab	Guideline	Actionable	Erbitux (cetuximab), alone and in combination with chemotherapy, is included in guidelines for patients with advanced or metastatic colon cancer that is BRAF wild-type, KRAS wild-type, and NRAS wild-type (NCCN.org).	detail...
IDH2 act mut	astrocytoma, IDH-mutant, grade 4	sensitive	Vorasidenib	Guideline	Actionable	Voranigo (vorasidenib) is included in guidelines for patients with recurrent or progressive (category 2B) WHO grade 4 astrocytoma harboring an IDH2 activating mutation (NCCN.org).	detail...
FLT3 rearrange	myeloid neoplasm	sensitive	Sorafenib	Guideline	Actionable	Nexavar (sorafenib) is included in guidelines for patients with a myeloid/lymphoid neoplasm with eosinophilia harboring a FLT3 rearrangement (NCCN.org).	detail...
MSH6 negative	cervical cancer	sensitive	Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab) is included in guidelines as preferred second-line or subsequent therapy for patients with cervical cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
BRAF fusion	skin melanoma	sensitive	Trametinib	Guideline	Actionable	Mekinist (trametinib) is included in guidelines as second-line therapy for metastatic or unresectable cutaneous melanoma patients with BRAF fusions (NCCN.org).	detail...
NTRK1 fusion	colon cancer	sensitive	Larotrectinib	Guideline	Actionable	Vitrakvi (larotrectinib) is included in guidelines for advanced or metastatic colon cancer patients with an NTRK fusion (NCCN.org).	detail...
RET fusion	esophagus squamous cell carcinoma	sensitive	Selpercatinib	Guideline	Actionable	Retevmo (selpercatinib) is included in guidelines as second-line or subsequent therapy for patients with locally advanced, recurrent, or metastatic esophageal squamous cell carcinoma harboring RET fusions (NCCN.org).	detail...
JAK1 rearrange	B-cell acute lymphoblastic leukemia	not applicable	N/A	Guideline	Prognostic	JAK1 rearrangements are associated with a poor prognosis in patients with B-cell acute lymphoblastic leukemia (NCCN.org).	detail...
FLT3 exon 15 ins	acute myeloid leukemia	sensitive	Midostaurin	Guideline	Actionable	Rydapt (midostaurin) is included in guidelines as maintenance therapy for patients with acute myeloid leukemia harboring a FLT3 internal tandem duplication (FLT3-ITD) mutation (NCCN.org).	detail...
MLH1 negative	endometrial carcinoma	sensitive	Nivolumab	Guideline	Actionable	Opdivo (nivolumab) is included in guidelines as a second-line or subsequent-line therapy for patients with high microsatellite instability (MSI-H) or mismatch repair deficient (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) recurrent endometrial carcinoma (NCCN.org).	detail...
PTEN mutant	skin melanoma	not applicable	N/A	Guideline	Risk Factor	Germline PTEN mutations or polymorphisms are associated with increased risk of developing single or multiple primary cutaneous melanomas (NCCN.org).	detail...
NTRK1 fusion	Squamous Cell Carcinoma of Unknown Primary	sensitive	Repotrectinib	Guideline	Actionable	Augtyro (repotrectinib) is included in guidelines for patients with squamous cell carcinoma of unknown primary harboring NTRK1 fusions (NCCN.org).	detail...
NTRK2 fusion	vaginal carcinoma	sensitive	Repotrectinib	Guideline	Actionable	Augtyro (repotrectinib) is included in guidelines as second-line or subsequent therapy for patients with recurrent or metastatic vaginal squamous cell carcinoma or adenocarcinoma harboring an NTRK fusion who are naive to prior NTRK targeted therapy or have progressed on prior NTRK therapy (NCCN.org).	detail...
BRAF V600E	pancreatic adenocarcinoma	sensitive	Dabrafenib + Trametinib	Guideline	Actionable	Tafinlar (dabrafenib) plus Mekinist (trametinib) is included in guidelines as first-line therapy for pancreatic adenocarcinoma patients harboring BRAF V600E with locally advanced or metastatic disease with good (ECOG 0-1) or intermediate (ECOG 2) performance status (PS) (category 2A), as first-line therapy in patients metastatic disease with poor (ECOG 3) PS (category 2B), and as subsequent-line therapy for patients with locally advanced, recurrent, or metastatic disease (category 2A) (NCCN.org).	detail...
NTRK2 fusion	vulva squamous cell carcinoma	sensitive	Repotrectinib	Guideline	Actionable	Augtyro (repotrectinib) is included in guidelines as a second-line or subsequent therapy for patients with advanced or recurrent/metastatic vulvar squamous cell carcinoma harboring an NTRK fusion (NCCN.org).	detail...
BRAF V600E	Adenocarcinoma of Unknown Primary	sensitive	Dabrafenib + Trametinib	Guideline	Actionable	The combination of Tafinlar (dabrafenib) and Mekinist (trametinib) is included in guidelines for patients with adenocarcinoma of unknown primary harboring BRAF V600E (NCCN.org).	detail...
NTRK1 fusion	vaginal carcinoma	sensitive	Repotrectinib	Guideline	Actionable	Augtyro (repotrectinib) is included in guidelines as second-line or subsequent therapy for patients with recurrent or metastatic vaginal squamous cell carcinoma or adenocarcinoma harboring an NTRK fusion who are naive to prior NTRK targeted therapy or have progressed on prior NTRK therapy (NCCN.org).	detail...
MSH6 negative	colon cancer	sensitive	Nivolumab	Guideline	Actionable	Opdivo (nivolumab) is included in guidelines as primary or subsequent therapy for patients with advanced or metastatic colon cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
BRAF V600E	skin melanoma	sensitive	Vemurafenib	Guideline	Actionable	Zelboraf (vemurafenib) therapy is included in guidelines for cutaneous melanoma patients with unresectable or metastatic disease harboring BRAF V600 activating mutations, such as BRAF V600E, in cases where BRAF/MEK inhibitor combination therapy is contraindicated (NCCN.org).	detail...
NTRK1 fusion	low grade glioma	sensitive	Larotrectinib	Guideline	Actionable	Vitrakvi (larotrectinib) is included in guidelines for patients with recurrent or progressive low grade glioma harboring an NTRK fusion (NCCN.org).	detail...
MSH6 negative	colon cancer	sensitive	Avelumab	Guideline	Actionable	Bavencio (avelumab) is included in guidelines (category 2A) for patients with advanced or metastatic colon cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MSH6, MSH2, MLH1, or PMS2 expression by IHC) (NCCN.org).	detail...
NTRK2 fusion	endometrial carcinoma	sensitive	Larotrectinib	Guideline	Actionable	Vitrakvi (larotrectinib) is included in guidelines as a second-line or subsequent-line therapy (category 2A) for patients with recurrent endometrial carcinoma harboring an NTRK fusion (NCCN.org).	detail...
MSH6 negative	gallbladder cancer	sensitive	Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab) is included in guidelines as primary therapy and subsequent-line therapy for patients with unresectable or metastatic biliary tract cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC), including gallbladder cancer (NCCN.org).	detail...
JAK2 rearrange	childhood B-cell acute lymphoblastic leukemia	not applicable	N/A	Guideline	Prognostic	JAK2 rearrangements are associated with a poor prognosis in pediatric patients with B-cell acute lymphoblastic leukemia (NCCN.org).	detail...
FGFR3 act mut	oral cavity cancer	sensitive	Erdafitinib	Guideline	Actionable	Balversa (erdafitinib) is included in guidelines as subsequent-line therapy (category 2B) for patients with oral cavity cancer harboring FGFR mutations or fusions and with no alternative options (NCCN.org).	detail...
MSH6 negative	appendix adenocarcinoma	sensitive	Tislelizumab	Guideline	Actionable	Tevimbra (tislelizumab) is included in guidelines (category 2A) for patients with advanced or metastatic appendiceal adenocarcinoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
FLT3 exon 14 ins	acute myeloid leukemia	sensitive	Sorafenib	Guideline	Actionable	Nexavar (sorafenib) is included in guidelines as maintenance therapy for patients with acute myeloid leukemia harboring a FLT3 internal tandem duplication (FLT3-ITD) mutation (NCCN.org).	detail...
NTRK2 fusion	breast cancer	sensitive	Repotrectinib	Guideline	Actionable	Augtyro (repotrectinib) is included in guidelines for patients with recurrent unresectable or stage IV (M1) breast cancer harboring an NTRK fusion (NCCN.org).	detail...
ALK rearrange	anaplastic large cell lymphoma	sensitive	Ceritinib	Guideline	Actionable	Zykadia (ceritinib) is included in guidelines as initial, second-line, and subsequent therapy for patients with anaplastic large cell lymphoma harboring ALK rearrangements (NCCN.org).	detail...
NTRK2 fusion	esophagus adenocarcinoma	sensitive	Entrectinib	Guideline	Actionable	Rozlytrek (entrectinib) is included in guidelines as second-line or subsequent therapy for patients with unresectable locally advanced, recurrent, or metastatic esophageal adenocarcinoma with an NTRK fusion (NCCN.org).	detail...
FGFR2 fusion	pancreatic adenocarcinoma	sensitive	Erdafitinib	Guideline	Actionable	Balversa (erdafitinib) is included in guidelines as subsequent therapy for patients with recurrent or locally advanced, metastatic pancreatic adenocarcinoma harboring an FGFR2 fusion with good (ECOG 0-1), intermediate (ECOG 2), or poor (ECOG 3) performance status (NCCN.org).	detail...
BRAF V600E	small intestine adenocarcinoma	sensitive	Encorafenib + Panitumumab	Guideline	Actionable	Braftovi (encorafenib) in combination with Vectibix (panitumumab) is included in guidelines as second-line or subsequent therapy (category 2A) for patients with advanced or metastatic small bowel adenocarcinoma harboring BRAF V600E (NCCN.org).	detail...
CTNNB1 mutant	desmoid tumor	not applicable	N/A	Guideline	Diagnostic	CTNNB1 mutations aid the diagnosis of desmoid tumor (NCCN.org).	detail...
NTRK1 fusion	salivary gland cancer	sensitive	Larotrectinib	Guideline	Actionable	Vitrakvi (larotrectinib) is included in guidelines for patients with NTRK1 fusion-positive salivary gland tumors with distant metastases (NCCN.org).	detail...
MSH6 negative	stomach cancer	sensitive	Fluorouracil + Oxaliplatin + Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab), in combination with Adrucil (fluorouracil) and Eloxatin (oxaliplatin) is included in guidelines as first-line therapy for patients with unresectable locally advanced, recurrent, or metastatic gastric cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
KMT2A rearrange	childhood B-cell acute lymphoblastic leukemia	not applicable	N/A	Guideline	Prognostic	KMT2A rearrangements are associated with a poor prognosis in pediatric patients with B-cell acute lymphoblastic leukemia (NCCN.org).	detail...
MSH6 negative	small intestine adenocarcinoma	sensitive	Ipilimumab + Nivolumab	Guideline	Actionable	Opdivo (nivolumab) in combination with Yervoy (ipilimumab) is included in guidelines as systemic therapy (category 2A) for patients with advanced or metastatic small bowel adenocarcinoma with deficient mismatch repair (dMMR, often defined by the loss of MSH6, MSH2, PMS2, or MLH1 expression by IHC) (NCCN.org).	detail...
RET C618X	medullary thyroid carcinoma	not applicable	N/A	Guideline	Risk Factor	Germline RET C618X mutations result in multiple endocrine neoplasia, type 2A (MEN 2A), which is associated with high risk of developing thyroid medullary carcinoma (NCCN.org).	detail...
FLT3 D835X	myelodysplastic syndrome	not applicable	N/A	Guideline	Prognostic	FLT3 D835 mutations are associated with poor prognosis in patients with myelodysplastic syndromes (NCCN.org).	detail...
RET C634X	medullary thyroid carcinoma	not applicable	N/A	Guideline	Risk Factor	Germline RET C634X mutations result in multiple endocrine neoplasia, type 2A (MEN 2A), which is associated with high risk of developing thyroid medullary carcinoma (NCCN.org).	detail...
FLT3 rearrange	myeloid neoplasm	sensitive	Sunitinib	Guideline	Actionable	Sutent (sunitinib) is included in guidelines for patients with a myeloid/lymphoid neoplasm with eosinophilia harboring a FLT3 rearrangement (NCCN.org).	detail...
BRAF V600E	skin melanoma	sensitive	Dabrafenib	Guideline	Actionable	Tafinlar (dabrafenib) therapy is included in guidelines for cutaneous melanoma patients with unresectable or metastatic disease harboring BRAF V600 activating mutations, such as BRAF V600E, in cases where BRAF/MEK inhibitor combination therapy is contraindicated (NCCN.org).	detail...
NTRK2 fusion	small intestine adenocarcinoma	sensitive	Entrectinib	Guideline	Actionable	Rozlytrek (entrectinib) is included in guidelines for patients with metastatic small bowel adenocarcinoma with an NTRK fusion (NCCN.org).	detail...
IDH1 mutant	myelodysplastic syndrome	sensitive	Azacitidine + Ivosidenib	Guideline	Actionable	Tibsovo (ivosidenib) in combination with Vidaza (azacitidine) is included in guidelines (category 2B) for patients with higher-risk myelodysplastic syndrome harboring an IDH1 mutation (NCCN.org).	detail...
FLT3 mutant	acute myeloid leukemia	sensitive	Azacitidine + Venetoclax	Guideline	Actionable	Venclexta (venetoclax) in combination with Vidaza (azacitidine) is included in guidelines for adult patients with acute myeloid leukemia harboring a FLT3 mutation (NCCN.org).	detail...
FGFR3 act mut	ethmoid sinus cancer	sensitive	Erdafitinib	Guideline	Actionable	Balversa (erdafitinib) is included in guidelines as subsequent-line therapy (category 2B) for patients with ethmoid sinus cancer harboring FGFR mutations or fusions and with no alternative options (NCCN.org).	detail...
FGFR3 fusion	breast cancer	sensitive	Erdafitinib	Guideline	Actionable	Balversa (erdafitinib) is included in guidelines for patients with stage IV (M1) breast cancer harboring FGFR fusion or mutations (category 2B) (NCCN.org).	detail...
FLT3 exon 14 ins	acute myeloid leukemia	sensitive	Cytarabine + Idarubicin + Quizartinib	Guideline	Actionable	Vanflyta (quizartinib) in combination with Idamycin (idarubicin) and Cytosar-U (cytarabine) is included in guidelines for patients with acute myeloid leukemia harboring a FLT3 internal tandem duplication (FLT3-ITD) mutation (NCCN.org).	detail...
NTRK2 fusion	anaplastic thyroid carcinoma	sensitive	Entrectinib	Guideline	Actionable	Rozlytrek (entrectinib) is included in guidelines as neoadjuvant treatment for anaplastic thyroid carcinoma patients harboring NTRK fusions with stage IVa or IVb borderline resectable disease, and as a preferred systemic therapy for those with metastatic disease (NCCN.org).	detail...
NTRK2 fusion	anaplastic thyroid carcinoma	sensitive	Repotrectinib	Guideline	Actionable	Augtyro (repotrectinib) is included in guidelines as neoadjuvant treatment for anaplastic thyroid carcinoma patients harboring NTRK fusions with stage IVa or IVb borderline resectable disease, and as a preferred systemic therapy for those with metastatic disease (NCCN.org).	detail...
FGFR3 fusion	oropharynx cancer	sensitive	Erdafitinib	Guideline	Actionable	Balversa (erdafitinib) is included in guidelines as subsequent-line therapy (category 2B) for patients with oropharynx cancer harboring FGFR mutations or fusions and with no alternative options (NCCN.org).	detail...
FGFR1 act mut	ethmoid sinus cancer	sensitive	Erdafitinib	Guideline	Actionable	Balversa (erdafitinib) is included in guidelines as subsequent-line therapy (category 2B) for patients with ethmoid sinus cancer harboring FGFR mutations or fusions and with no alternative options (NCCN.org).	detail...
BRAF fusion	pilocytic astrocytoma	not applicable	N/A	Guideline	Diagnostic	BRAF fusions aid in the diagnosis of pilocytic astrocytoma (NCCN.org).	detail...
NTRK2 fusion	hepatocellular carcinoma	sensitive	Entrectinib	Guideline	Actionable	Rozlytrek (entrectinib) is included in guidelines as subsequent-line therapy for patients with hepatocellular carcinoma harboring an NTRK fusion (NCCN.org).	detail...
PDGFRB rearrange	myeloid and lymphoid neoplasms associated with PDGFRB rearrangement	sensitive	Imatinib	Guideline	Actionable	Gleevec (imatinib) is included in guidelines for patients with a myeloid/lymphoid neoplasm with eosinophilia harboring a PDGFRB rearrangement (NCCN.org).	detail...
MSH6 negative	medullary thyroid carcinoma	sensitive	Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab) is included in guidelines for patients with medullary thyroid carcinoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) after progression on prior treatment (NCCN.org).	detail...
NTRK1 fusion	colon cancer	sensitive	Repotrectinib	Guideline	Actionable	Augtyro (repotrectinib) is included in guidelines as second-line or subsequent therapy (category 2A) for patients with advanced or metastatic colon cancer harboring an NTRK fusion (NCCN.org).	detail...
FLT3 exon17	acute myeloid leukemia	sensitive	Midostaurin	Guideline	Actionable	Rydapt (midostaurin) is included in guidelines as maintenance therapy for patients with acute myeloid leukemia harboring a mutation in the FLT3 tyrosine kinase domain (exons 14-23) (NCCN.org).	detail...
ALK rearrange	lung non-small cell carcinoma	no benefit	Durvalumab	Guideline	Actionable	Monotherapy with immune checkpoint inhibitors, including Opdivo (nivolumab), Keytruda (pembrolizumab), Tecentriq (atezolizumab), and Imfinzi (durvalumab), is not indicated for use as initial systemic therapy or subsequent therapy in non-small cell lung cancer patients harboring oncogenic drivers, including ALK rearrangement (NCCN.org).	detail...
FGFR1 act mut	maxillary sinus cancer	sensitive	Erdafitinib	Guideline	Actionable	Balversa (erdafitinib) is included in guidelines as subsequent-line therapy (category 2B) for patients with maxillary sinus cancer harboring FGFR mutations or fusions and with no alternative options (NCCN.org).	detail...
MLH1 negative	ovary epithelial cancer	sensitive	Dostarlimab-gxly	Guideline	Actionable	Jemperli (dostarlimab-gxly) is included in guidelines as systemic therapy for patients with recurrent or advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
FLT3 exon 14 ins	acute myeloid leukemia	sensitive	Cytarabine + Midostaurin	Guideline	Actionable	Rydapt (midostaurin) in combination with Cytosar-U (cytarabine) is included in guidelines as consolidation therapy for patients with acute myeloid leukemia harboring a FLT3 internal tandem duplication (FLT3-ITD) mutation (NCCN.org).	detail...
MLH1 negative	small intestine adenocarcinoma	sensitive	Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab) is included in guidelines as systemic therapy (category 2A) for patients with advanced or metastatic small bowel adenocarcinoma with deficient mismatch repair (dMMR, often defined by the loss of MLH1, MSH2, MSH6, or PMS2 expression by IHC) (NCCN.org).	detail...
MLH1 negative	colon cancer	sensitive	Penpulimab-kcqx	Guideline	Actionable	Penpulimab-kcqx (AK105) is included in guidelines (category 2A) for patients with advanced or metastatic colon cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, MSH6, MSH2, or PMS2 expression by IHC) (NCCN.org).	detail...
MLH1 negative	neuroendocrine tumor	sensitive	Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab) is included in guidelines for patients with mismatch repair deficient (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) locally advanced or metastatic well-differentiated, Grade 3 neuroendocrine tumors or unresectable or metastatic extrapulmonary poorly differentiated neuroendocrine carcinoma, large or small cell carcinoma, or mixed neuroendocrine/non-neuroendocrine neoplasms who have progressed on or following prior treatment (NCCN.org).	detail...
BRAF V600E/K	skin melanoma	sensitive	Binimetinib + Encorafenib	Guideline	Actionable	Braftovi (encorafenib) in combination with Mektovi (binimetinib) is included in guidelines as first-line and second-line therapy for patients with metastatic or unresectable cutaneous melanoma harboring BRAF V600E or V600K mutations (PMID: 30959471; NCCN.org).	30959471 detail...
MSH6 negative	extrahepatic bile duct carcinoma	sensitive	Dostarlimab-gxly	Guideline	Actionable	Jemperli (dostarlimab-gxly) is included in guidelines as subsequent therapy (category 2B) for patients with biliary tract cancer with deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC), including extrahepatic cholangiocarcinoma (NCCN.org).	detail...
MSH6 negative	esophagus squamous cell carcinoma	sensitive	Fluorouracil + Oxaliplatin + Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab), in combination with Adrucil (fluorouracil) and Eloxatin (oxaliplatin) is included in guidelines as first-line therapy for patients with unresectable locally advanced, recurrent, or metastatic esophagus squamous cell carcinoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
IDH2 R140Q	myelodysplastic syndrome	not applicable	N/A	Guideline	Prognostic	IDH2 R140Q is associated with a poor prognosis in patients with myelodysplastic syndrome (NCCN.org).	detail...
FGFR3 act mut	glioblastoma	sensitive	Erdafitinib	Guideline	Actionable	Balversa (erdafitinib) is included in guidelines (category 2B) for patients with recurrent or progressive glioblastoma harboring FGFR mutations or fusions with no alternative treatment options (NCCN.org).	detail...
MSH6 negative	gastroesophageal junction adenocarcinoma	sensitive	Fluorouracil + Oxaliplatin + Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab), in combination with Adrucil (fluorouracil) and Eloxatin (oxaliplatin) is included in guidelines as first-line therapy for patients with unresectable locally advanced, recurrent, or metastatic gastroesophageal junction adenocarcinoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
NTRK2 fusion	salivary gland cancer	sensitive	Entrectinib	Guideline	Actionable	Rozlytrek (entrectinib) is included in guidelines for patients with NTRK2 fusion-positive salivary gland tumors with distant metastases (NCCN.org).	detail...
BRAF V600E	anaplastic thyroid carcinoma	sensitive	Dabrafenib + Trametinib	Guideline	Actionable	Tafinlar (dabrafenib) and Mekinist (trametinib) combination therapy is included in guidelines as neoadjuvant treatment for anaplastic thyroid carcinoma patients harboring BRAF V600E with tage IVa or IVb borderline resectable disease, and as a preferred systemic therapy for those with metastatic disease (NCCN.org).	detail...
ALK rearrange	anaplastic large cell lymphoma	sensitive	Alectinib	Guideline	Actionable	Alecensa (alectinib) is included in guidelines as second-line and subsequent therapy for patients with anaplastic large cell lymphoma harboring ALK rearrangements (NCCN.org).	detail...
NTRK1 fusion	vaginal carcinoma	sensitive	Entrectinib	Guideline	Actionable	Rozlytrek (entrectinib) is included in guidelines as second-line or subsequent therapy for patients with recurrent or metastatic vaginal squamous cell carcinoma or adenocarcinoma harboring an NTRK fusion (NCCN.org).	detail...
MSH6 negative	rectum cancer	sensitive	Ipilimumab + Nivolumab	Guideline	Actionable	Opdivo (nivolumab) in combination with Yervoy (ipilimumab) is included in guidelines as a primary therapy for advanced or metastatic rectum cancer patients with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
MLH1 negative	endometrial carcinoma	sensitive	Tislelizumab	Guideline	Actionable	Tevimbra (tislelizumab) is included in guidelines as a second-line or subsequent-line therapy for patients with high microsatellite instability (MSI-H) or mismatch repair deficient (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) recurrent endometrial carcinoma (NCCN.org).	detail...
JAK2 rearrange	myeloid neoplasm	sensitive	Pacritinib	Guideline	Actionable	Vonjo (pacritinib) is included in guidelines for patients with a myeloid/lymphoid neoplasm with eosinophilia harboring a JAK2 rearrangement (NCCN.org).	detail...
ROS1 rearrange	lung non-small cell carcinoma	sensitive	Lorlatinib	Guideline	Actionable	Lorbrena (lorlatinib) is included in guidelines as subsequent therapy in patients with advanced or metastatic ROS1-rearranged non-small lung cancer (NCCN.org).	detail...
BRAF rearrange	subependymal giant cell astrocytoma	sensitive	Tovorafenib	Guideline	Actionable	Ojemda (tovorafenib) is included in guidelines (category 2A) for patients with recurrent or progressive circumscribed glioma, including subependymal giant cell astrocytoma, harboring BRAF fusions, rearrangements, or BRAF V600 mutations (NCCN.org).	detail...
NTRK1 fusion	ampulla of Vater adenocarcinoma	sensitive	Larotrectinib	Guideline	Actionable	Vitrakvi (larotrectinib) is included in guidelines as first-line or subsequent therapy for patients with metastatic ampullary adenocarcinoma harboring NTRK fusions (NCCN.org).	detail...
FLT3 exon20	acute myeloid leukemia	sensitive	Cytarabine + Daunorubicin + Midostaurin	Guideline	Actionable	Rydapt (midostaurin), in combination with Cerubidine (daunorubicin) and Cytosar-U (cytarabine), is included in guidelines for patients with acute myeloid leukemia harboring a mutation in the FLT3 tyrosine kinase domain (exons 14-23) (NCCN.org).	detail...
KIT D816V	systemic mastocytosis	not applicable	N/A	Guideline	Prognostic	KIT D816V is associated with an adverse prognosis in patients with systemic mastocytosis (NCCN.org).	detail...
BRAF V600E	anaplastic oligodendroglioma	sensitive	Cobimetinib + Vemurafenib	Guideline	Actionable	Combination of Zelboraf (vemurafenib) and Cotellic (cobimetinib) is included in guidelines for patients with recurrent anaplastic gliomas harboring BRAF V600E, including anaplastic oligodendroglioma (NCCN.org).	detail...
BRAF V600E	lung non-small cell carcinoma	sensitive	Vemurafenib	Guideline	Actionable	Zelboraf (vemurafenib) is included in guidelines as a first-line therapy for advanced or metastatic non-small cell lung cancer patients harboring BRAF V600E mutations who can not tolerate the combination of Mekinist (trametinib) and Tafinlar (dabrafenib) (NCCN.org).	detail...
BRAF V600E	low grade glioma	sensitive	Dabrafenib + Trametinib	Guideline	Actionable	Combination of Mekinist (trametinib) and Tafinlar (dabrafenib) is included in guidelines for patients with recurrent or progressive low grade glioma harboring BRAF V600E (NCCN.org).	detail...
FGFR2 act mut	ethmoid sinus cancer	sensitive	Erdafitinib	Guideline	Actionable	Balversa (erdafitinib) is included in guidelines as subsequent-line therapy (category 2B) for patients with ethmoid sinus cancer harboring FGFR mutations or fusions and with no alternative options (NCCN.org).	detail...
NTRK1 fusion	vulva adenocarcinoma	sensitive	Larotrectinib	Guideline	Actionable	Vitrakvi (larotrectinib) is included in guidelines as a second-line or subsequent therapy for patients with advanced or recurrent/metastatic vulvar adenocarcinoma harboring an NTRK fusion (NCCN.org).	detail...
FGFR2 fusion	cholangiocarcinoma	sensitive	Pemigatinib	Guideline	Actionable	Pemazyre (pemigatinib) is included in guidelines as subsequent-line therapy for patients with cholangiocarcinoma harboring FGFR2 fusions or rearrangements (NCCN.org).	detail...
MLH1 negative	colon cancer	sensitive	Atezolizumab	Guideline	Actionable	Tecentriq (atezolizumab) is included in guidelines (category 2A) for patients with advanced or metastatic colon cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, MSH2, MSH6, or PMS2 expression by IHC) (NCCN.org).	detail...
BRAF V600E	rectum cancer	sensitive	Capecitabine + Cetuximab + Encorafenib + Oxaliplatin	Guideline	Actionable	Braftovi (encorafenib) in combination with Erbitux (cetuximab) and CAPEOX is included in guidelines as an initial therapy (category 2A) for patients with advanced or metastatic rectal cancer harboring BRAF V600E (NCCN.org).	detail...
MLH1 negative	small intestine adenocarcinoma	sensitive	Durvalumab	Guideline	Actionable	Imfinzi (durvalumab) is included in guidelines as systemic therapy (category 2A) for patients with advanced or metastatic small bowel adenocarcinoma with deficient mismatch repair (dMMR, often defined by the loss of MLH1, MSH2, MSH6, or PMS2 expression by IHC) (NCCN.org).	detail...
FGFR1 rearrange	myeloid and lymphoid neoplasms associated with FGFR1 abnormalities	sensitive	Pemigatinib	Guideline	Actionable	Pemazyre (pemigatinib) is included in guidelines (category 2A) for patients with a myeloid/lymphoid neoplasm with eosinophilia harboring an FGFR1 rearrangement (NCCN.org).	detail...
MSH6 negative	small intestine adenocarcinoma	sensitive	Atezolizumab + Fluorouracil + Leucovorin + Oxaliplatin	Guideline	Actionable	Tecentriq (atezolizumab) in combination with Adrucil (fluorouracil), Wellcovorin (leucovorin), and Eloxatin (oxaliplatin) is included in guidelines as adjuvant therapy (category 2A) for patients with small bowel adenocarcinoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MSH6, MSH2, MLH1, or PMS2 expression by IHC) (NCCN.org).	detail...
NTRK2 fusion	intrahepatic cholangiocarcinoma	sensitive	Repotrectinib	Guideline	Actionable	Augtyro (repotrectinib) is included in guidelines as primary and subsequent-line therapy (category 2A) for patients with unresectable or metastatic biliary tract cancer harboring NTRK fusions, including intrahepatic cholangiocarcinoma (NCCN.org).	detail...
MSH6 negative	stomach cancer	sensitive	Durvalumab + Tremelimumab	Guideline	Actionable	Imfinzi (durvalumab), in combination with Imjudo (tremelimumab, is included in guidelines as neoadjuvant therapy for patients with gastric cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
MLH1 mutant	pancreatic cancer	not applicable	N/A	Guideline	Risk Factor	Germline mutations in MLH1 result in Lynch syndrome, which is associated with increased risk of developing pancreatic cancer (NCCN.org).	detail...
ALK rearrange	lung non-small cell carcinoma	sensitive	Ensartinib	Guideline	Actionable	Ensacove (ensartinib) is included in guidelines as preferred first-line therapy (category 1) and as subsequent therapy for patients with ALK-rearranged advanced or metastatic non-small cell lung cancer (NCCN.org).	detail...
FLT3 exon23	acute myeloid leukemia	sensitive	Gilteritinib	Guideline	Actionable	Xospata (gilteritinib) is included in guidelines for patients with relapsed or refractory acute myeloid leukemia harboring a mutation in the FLT3 tyrosine kinase domain (exons 14-23) (NCCN.org).	detail...
TP53 mutant	chronic lymphocytic leukemia/small lymphocytic lymphoma	sensitive	Idelalisib	Guideline	Actionable	Zydelig (idelalisib) is included in the guidelines for patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma with a TP53 mutation after prior BTK inhibitor-based and BCL2 inhibitor-containing regimens (NCCN.org).	detail...
NTRK1 fusion	subependymal giant cell astrocytoma	sensitive	Repotrectinib	Guideline	Actionable	Augtyro (repotrectinib) is included in guidelines (category 2B) for patients with recurrent or progressive circumscribed glioma, including subependymal giant cell astrocytoma, harboring an NTRK fusion (NCCN.org).	detail...
ALK fusion	Erdheim-Chester disease	sensitive	Alectinib	Guideline	Actionable	Alecensa (alectinib) is included in guidelines as first-line or subsequent-line therapy for patients with Erdheim-Chester disease harboring ALK fusions (NCCN.org).	detail...
NTRK1 fusion	esophagus adenocarcinoma	sensitive	Larotrectinib	Guideline	Actionable	Vitrakvi (larotrectinib) is included in guidelines as second-line or subsequent therapy for patients with unresectable locally advanced, recurrent, or metastatic esophageal adenocarcinoma with an NTRK fusion (NCCN.org).	detail...
MLH1 negative	esophagus squamous cell carcinoma	sensitive	Fluorouracil + Nivolumab + Oxaliplatin	Guideline	Actionable	Opdivo (nivolumab), in combination with Adrucil (fluorouracil) and Eloxatin (oxaliplatin) is included in guidelines as first-line therapy for patients with unresectable locally advanced, recurrent, or metastatic esophagus squamous cell carcinoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
ROS1 rearrange	lung non-small cell carcinoma	sensitive	Taletrectinib	Guideline	Actionable	Ibtrozi (taletrectinib) is included in guidelines as preferred first-line or subsequent therapy for patients with advanced or metastatic non-small cell lung cancer harboring a ROS1 rearrangement (NCCN.org).	detail...
ALK rearrange	inflammatory myofibroblastic tumor	sensitive	Lorlatinib	Guideline	Actionable	Lorbrena (lorlatinib) is included in guidelines as first-line therapy for patients with advanced, recurrent, metastatic, or inoperable inflammatory myofibroblastic tumor harboring ALK translocations (NCCN.org).	detail...
NTRK1 fusion	neuroendocrine tumor	sensitive	Entrectinib	Guideline	Actionable	Rozlytrek (entrectinib) is included in guidelines for patients with unresectable or metastatic extrapulmonary poorly differentiated neuroendocrine carcinoma, large or small cell carcinoma, or mixed neuroendocrine/non-neuroendocrine neoplasms harboring an NTRK fusion who have progressed on or following prior treatment (NCCN.org).	detail...
JAK3 mutant	childhood B-cell acute lymphoblastic leukemia	not applicable	N/A	Guideline	Prognostic	JAK3 mutations are associated with a poor prognosis in pediatric patients with B-cell acute lymphoblastic leukemia (NCCN.org).	detail...
FLT3 exon 15 ins	acute myeloid leukemia	sensitive	Cytarabine + Idarubicin + Quizartinib	Guideline	Actionable	Vanflyta (quizartinib) in combination with Idamycin (idarubicin) and Cytosar-U (cytarabine) is included in guidelines (category 1) for patients with acute myeloid leukemia harboring a FLT3 internal tandem duplication (FLT3-ITD) mutation (NCCN.org).	detail...
NTRK2 fusion	neuroendocrine tumor	sensitive	Repotrectinib	Guideline	Actionable	Augtyro (repotrectinib) is included in guidelines for patients with unresectable or metastatic extrapulmonary poorly differentiated neuroendocrine carcinoma, large or small cell carcinoma, or mixed neuroendocrine/non-neuroendocrine neoplasms harboring an NTRK fusion who have progressed on a prior NTRK-targeted therapy (NCCN.org).	detail...
TP53 mutant	adrenocortical carcinoma	not applicable	N/A	Guideline	Risk Factor	Germline TP53 mutations result in Li-Fraumeni syndrome, which is associated with increased risk of developing adrenocortical carcinoma (NCCN.org).	detail...
VHL inact mut	clear cell renal cell carcinoma	not applicable	N/A	Guideline	Risk Factor	Germline inactivating mutations in VHL result in von Hippel-Lindau (VHL) syndrome, which is associated with increased risk of developing clear cell renal cell carcinoma (NCCN.org).	detail...
BRAF V600E	papillary thyroid carcinoma	sensitive	Vemurafenib	Guideline	Actionable	Zelboraf (vemurafenib) is included in guidelines for patients with RAI-refractory papillary thyroid carcinoma harboring BRAF V600E for whom clinical trials or other systemic therapies are not available or appropriate (category 2B) (NCCN.org).	detail...
MLH1 negative	colon cancer	sensitive	Cemiplimab	Guideline	Actionable	Libtayo (cemiplimab) is included in guidelines (category 2A) for patients with advanced or metastatic colon cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
MSH6 negative	gastroesophageal junction adenocarcinoma	sensitive	Durvalumab + Tremelimumab	Guideline	Actionable	Imfinzi (durvalumab), in combination with Imjudo (tremelimumab), is included in guidelines as neoadjuvant therapy for patients with gastroesophageal junction adenocarcinoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
BRAF V600E	small intestine adenocarcinoma	sensitive	Dabrafenib + Trametinib	Guideline	Actionable	Tafinlar (dabrafenib) in combination with Mekinist (trametinib) is included in guidelines for patients with advanced or metastatic small bowel adenocarcinoma harboring BRAF V600E (NCCN.org).	detail...
NTRK1 fusion	lung non-small cell carcinoma	sensitive	Entrectinib	Guideline	Actionable	Rozlytrek (entrectinib) is included in guidelines as first-line or subsequent therapy for patients with advanced or metastatic non-small cell lung cancer harboring an NTRK1 fusion (NCCN.org).	detail...
BRAF V600E	rectum cancer	sensitive	Encorafenib + Fluorouracil + Irinotecan + Leucovorin + Panitumumab	Guideline	Actionable	Braftovi (encorafenib) in combination with Vectibix (panitumumab) and FOLFIRI is included in guidelines as a preferred initial therapy (category 2A) for patients with advanced or metastatic rectal cancer harboring BRAF V600E (NCCN.org).	detail...
TP53 loss	chronic lymphocytic leukemia/small lymphocytic lymphoma	sensitive	Lenalidomide + Rituximab	Guideline	Actionable	Revlimid (lenalidomide) combined with Rituxan (rituximab) is included in guidelines for patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma with TP53 loss after prior BTK inhibitor-based and BCL2 inhibitor-containing regimens (NCCN.org).	detail...
FLT3 exon18	acute myeloid leukemia	sensitive	Cytarabine + Daunorubicin + Midostaurin	Guideline	Actionable	Rydapt (midostaurin), in combination with Cerubidine (daunorubicin) and Cytosar-U (cytarabine), is included in guidelines for patients with acute myeloid leukemia harboring a mutation in the FLT3 tyrosine kinase domain (exons 14-23) (NCCN.org).	detail...
BRAF V600E	biliary tract cancer	sensitive	Dabrafenib + Trametinib	Guideline	Actionable	Tafinlar (dabrafenib) in combination with Mekinist (trametinib) is included in guidelines as subsequent-line therapy for patients with biliary tract cancer harboring BRAF V600E, including intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gallbladder cancer (NCCN.org).	detail...
TP53 loss	chronic lymphocytic leukemia/small lymphocytic lymphoma	sensitive	Idelalisib	Guideline	Actionable	Zydelig (idelalisib) is included in guidelines for patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma with TP53 loss after prior BTK inhibitor-based and BCL2 inhibitor-containing regimens (NCCN.org).	detail...
RET fusion	esophagus adenocarcinoma	sensitive	Selpercatinib	Guideline	Actionable	Retevmo (selpercatinib) is included in guidelines as second-line or subsequent therapy for patients with locally advanced, recurrent, or metastatic esophageal adenocarcinoma harboring RET fusions (NCCN.org).	detail...
IDH2 act mut	astrocytoma, IDH-mutant, grade 2	sensitive	Vorasidenib	Guideline	Actionable	Voranigo (vorasidenib) is included in guidelines for patients with WHO grade 2 astrocytoma harboring an IDH2 activating mutation with no residual/measurable disease or as adjuvant therapy after surgery/biopsy (category 1) and for patients with recurrent or progressive disease (category 2A) (NCCN.org).	detail...
APC mutant	small intestine adenocarcinoma	not applicable	N/A	Guideline	Risk Factor	Familial adenomatous polyposis results from germline mutations in the APC gene, and is associated with increased risk of developing small bowel adenocarcinoma (NCCN.org).	detail...
MLH1 negative	rectum cancer	sensitive	Atezolizumab	Guideline	Actionable	Tecentriq (atezolizumab) is included in guidelines (category 2A) for patients with advanced or metastatic rectal cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, MSH2, MSH6, or PMS2 expression by IHC) (NCCN.org).	detail...
VHL inact mut	renal cell carcinoma	sensitive	Belzutifan	Guideline	Actionable	Welireg (belzutifan) is included in guidelines for patients with Von Hippel-Lindau disease-associated renal cell carcinoma that do not require immediate surgery (NCCN.org).	detail...
NTRK2 fusion	vulva adenocarcinoma	sensitive	Larotrectinib	Guideline	Actionable	Vitrakvi (larotrectinib) is included in guidelines as a second-line or subsequent therapy for patients with advanced or recurrent/metastatic vulvar adenocarcinoma harboring an NTRK fusion (NCCN.org).	detail...
MLH1 negative	oropharynx cancer	sensitive	Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab) is included in guidelines as first- and subsequent-line therapy for patients with mismatch repair deficient (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) recurrent, unresectable, or metastatic oropharynx cancer (NCCN.org).	detail...
BRAF V600E	colon cancer	sensitive	Encorafenib + Fluorouracil + Irinotecan + Leucovorin + Panitumumab	Guideline	Actionable	Braftovi (encorafenib) in combination with Vectibix (panitumumab) and FOLFIRI is included in guidelines as a preferred initial therapy (category 2A) for patients with advanced or metastatic colon cancer harboring BRAF V600E (NCCN.org).	detail...
FGFR2 fusion	breast cancer	sensitive	Erdafitinib	Guideline	Actionable	Balversa (erdafitinib) is included in guidelines for patients with stage IV (M1) breast cancer harboring FGFR fusion or mutations (category 2B) (NCCN.org).	detail...
FLT3 exon18	acute myeloid leukemia	sensitive	Cytarabine + Idarubicin + Midostaurin	Guideline	Actionable	Rydapt (midostaurin) in combination with Idamycin (idarubicin) and Cytosar-U (cytarabine) is included in guidelines for patients with acute myeloid leukemia harboring a mutation in the FLT3 tyrosine kinase domain (exons 14-23) (NCCN.org).	detail...
IDH1 mutant	acute myeloid leukemia	sensitive	Azacitidine + Venetoclax	Guideline	Actionable	Venclexta (venetoclax) in combination with Vidaza (azacitidine) is included in guidelines (category 1) for adult patients with acute myeloid leukemia harboring an IDH1 mutation (NCCN.org).	detail...
MSH6 negative	esophagus squamous cell carcinoma	sensitive	Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab) is included in guidelines as second-line or subsequent therapy for patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) esophageal squamous cell carcinoma that are unresectable, locally advanced, recurrent, or metastatic (NCCN.org).	detail...
RET fusion	oncocytic carcinoma of the thyroid	sensitive	Pralsetinib	Guideline	Actionable	Gavreto (pralsetinib) is included in guidelines for patients with RAI-refractory oncocytic thyroid carcinoma harboring a RET fusion with progressive or symptomatic disease (NCCN.org).	detail...
NTRK1 fusion	rectum cancer	sensitive	Entrectinib	Guideline	Actionable	Rozlytrek (entrectinib) is included in guidelines for advanced or metastatic rectal cancer patients with an NTRK fusion (NCCN.org).	detail...
RET fusion	endometrial carcinoma	sensitive	Selpercatinib	Guideline	Actionable	Retevmo (selpercatinib) is included in guidelines as a second-line or subsequent-line therapy for patients with recurrent endometrial carcinoma harboring RET fusions (NCCN.org).	detail...
IDH1 mutant	malignant astrocytoma	not applicable	N/A	Guideline	Diagnostic	IDH1 mutations aid in the diagnosis of grade II and grade III astrocytomas (NCCN.org).	detail...
KMT2A rearrange	B-cell acute lymphoblastic leukemia	sensitive	Revumenib	Guideline	Actionable	Revuforj (revumenib) is included in guidelines for patients with relapsed or refractory B-cell acute lymphoblastic leukemia harboring a KMT2A rearrangement (NCCN.org).	detail...
FLT3 exon21	acute myeloid leukemia	sensitive	Cytarabine + Daunorubicin + Midostaurin	Guideline	Actionable	Rydapt (midostaurin), in combination with Cerubidine (daunorubicin) and Cytosar-U (cytarabine), is included in guidelines for patients with acute myeloid leukemia harboring a mutation in the FLT3 tyrosine kinase domain (exons 14-23) (NCCN.org).	detail...
PTEN del	colon cancer	sensitive	Aspirin	Guideline	Actionable	Aspirin is included in guidelines as adjuvant therapy (category 2A) for patients with advanced colon cancer harboring deep PTEN deletions and other somatic mutations affecting the PI3K pathway genes PIK3CA, PIK3R1, or PTEN (NCCN.org).	detail...
MLH1 negative	small intestine adenocarcinoma	sensitive	Atezolizumab	Guideline	Actionable	Tecentriq (atezolizumab) is included in guidelines as systemic therapy (category 2A) for patients with advanced or metastatic small bowel adenocarcinoma with deficient mismatch repair (dMMR, often defined by the loss of MLH1, MSH2, MSH6, or PMS2 expression by IHC) (NCCN.org).	detail...
MSH6 negative	gastroesophageal junction adenocarcinoma	sensitive	Ipilimumab + Nivolumab	Guideline	Actionable	Opdivo (nivolumab), in combination with Yervoy (ipilimumab), is included in guidelines as first-line, second-line, or subsequent therapy for patients with unresectable locally advanced, recurrent, or metastatic gastroesophageal junction adenocarcinoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
NTRK1 fusion	esophagus adenocarcinoma	sensitive	Repotrectinib	Guideline	Actionable	Augtyro (repotrectinib) is included in guidelines as second-line or subsequent therapy for patients with unresectable locally advanced, recurrent, or metastatic esophageal adenocarcinoma with an NTRK fusion (NCCN.org).	detail...
KIT act mut	skin melanoma	sensitive	Imatinib	Guideline	Actionable	Gleevec (imatinib) is included in guidelines as second-line therapy for metastatic or unresectable cutaneous melanoma patients with KIT activating mutations (NCCN.org).	detail...
MLH1 negative	breast cancer	sensitive	Dostarlimab-gxly	Guideline	Actionable	Jemperli (dostarlimab-gxly) is included in guidelines for patients with recurrent unresectable or stage IV (M1) breast cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) who have progressed on or following prior treatment (NCCN.org).	detail...
BRAF V600E	high grade glioma	sensitive	Vemurafenib	Guideline	Actionable	Zelboraf (vemurafenib) is included in guidelines as adjuvant therapy for pediatric patients with diffuse high-grade gliomas harboring BRAF V600E, or as a preferred regimen for patients with recurrent or progressive disease (NCCN.org).	detail...
APC mutant	desmoid tumor	not applicable	N/A	Guideline	Diagnostic	APC mutations aid the diagnosis of desmoid tumor (NCCN.org).	detail...
ALK rearrange	lung non-small cell carcinoma	sensitive	Brigatinib	Guideline	Actionable	Alunbrig (brigatinib) is included in guidelines as preferred first-line (category 1) and as subsequent therapy for patients with advanced or metastatic ALK-rearranged non-small cell lung cancer (NCCN.org).	detail...
TP53 loss	chronic lymphocytic leukemia/small lymphocytic lymphoma	sensitive	Obinutuzumab	Guideline	Actionable	Gazyva (obinutuzumab) is included in guidelines as first-line therapy for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with TP53 loss (NCCN.org).	detail...
APC mutant	medulloblastoma	not applicable	N/A	Guideline	Prognostic	WNT-driven medulloblastomas, characterized by CTNNB1 or APC mutations, are associated with favorable prognosis (NCCN.org).	detail...
MLH1 negative	small intestine adenocarcinoma	sensitive	Ipilimumab + Nivolumab	Guideline	Actionable	Opdivo (nivolumab) in combination with Yervoy (ipilimumab) is included in guidelines as systemic therapy (category 2A) for patients with advanced or metastatic small bowel adenocarcinoma with deficient mismatch repair (dMMR, often defined by the loss of MLH1, MSH2, MSH6, or PMS2 expression by IHC) (NCCN.org).	detail...
MSH6 negative	ovarian germ cell cancer	sensitive	Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab) is included in guidelines as recurrence therapy for patients with malignant ovarian germ cell tumors with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
TP53 mutant	essential thrombocythemia	not applicable	N/A	Guideline	Prognostic	The presence of at least one mutation in either SH2B3, IDH2, U2AF1, SRSF2, SF3B1, EZH2, TP53, or RUNX1 is associated with inferior overall survival in patients with essential thrombocythemia (NCCN.org).	detail...
MLH1 negative	colon cancer	sensitive	Avelumab	Guideline	Actionable	Bavencio (avelumab) is included in guidelines (category 2A) for patients with advanced or metastatic colon cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, MSH2, MSH6, or PMS2 expression by IHC) (NCCN.org).	detail...
FLT3 exon21	acute myeloid leukemia	sensitive	Cytarabine + Idarubicin + Midostaurin	Guideline	Actionable	Rydapt (midostaurin) in combination with Idarubicin and Cytosar-U (cytarabine) is included in guidelines for patients with acute myeloid leukemia harboring a mutation in the FLT3 tyrosine kinase domain (exons 14-23) (NCCN.org).	detail...
IDH2 act mut	oligodendroglioma	sensitive	Vorasidenib	Guideline	Actionable	Voranigo (vorasidenib) is included in guidelines for patients with WHO grade 2 1p19q codeleted oligodendroglioma with residual/measurable disease after surgery/biopsy (category 1) or recurrent or progressive disease and WHO grade 3 1p19q codeleted oligodendroglioma with recurrent or progressive disease or as adjuvant treatment (category 2B) harboring an IDH2 activating mutation (NCCN.org).	detail...
MLH1 negative	esophagus adenocarcinoma	sensitive	Capecitabine + Nivolumab + Oxaliplatin	Guideline	Actionable	Opdivo (nivolumab), in combination with Xeloda (capecitabine) and Eloxatin (oxaliplatin) is included in guidelines as first-line therapy for patients with unresectable locally advanced, recurrent, or metastatic esophageal adenocarcinoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
JAK1 mutant	B-cell acute lymphoblastic leukemia	not applicable	N/A	Guideline	Prognostic	JAK1 mutations are associated with a poor prognosis in patients with B-cell acute lymphoblastic leukemia (NCCN.org).	detail...
FLT3 exon 15 ins	acute myeloid leukemia	sensitive	Cytarabine + Daunorubicin + Midostaurin	Guideline	Actionable	Rydapt (midostaurin) in combination with Cerubidine (daunorubicin) and Cytosar-U (cytarabine) is included in guidelines for patients with acute myeloid leukemia harboring a FLT3 internal tandem duplication (FLT3-ITD) mutation (NCCN.org).	detail...
NTRK2 fusion	lung non-small cell carcinoma	sensitive	Entrectinib	Guideline	Actionable	Rozlytrek (entrectinib) is included in guidelines as first-line or subsequent therapy for patients with advanced or metastatic non-small cell lung cancer harboring an NTRK2 fusion (NCCN.org).	detail...
MLH1 negative	stomach cancer	sensitive	Capecitabine + Oxaliplatin + Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab), in combination with Xeloda (capecitabine) and Eloxatin (oxaliplatin) is included in guidelines as first-line therapy for patients with unresectable locally advanced, recurrent, or metastatic gastric cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
MLH1 negative	stomach cancer	sensitive	Durvalumab + Tremelimumab	Guideline	Actionable	Imfinzi (durvalumab), in combination with Imjudo (tremelimumab, is included in guidelines as neoadjuvant therapy for patients with gastric cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
BRAF V600E	anaplastic astrocytoma	sensitive	Dabrafenib + Trametinib	Guideline	Actionable	Combination of Mekinist (trametinib) and Tafinlar (dabrafenib) is included in guidelines for patients with recurrent anaplastic gliomas harboring BRAF V600E, including anaplastic astrocytoma (NCCN.org).	detail...
IDH2 mutant	malignant astrocytoma	not applicable	N/A	Guideline	Diagnostic	IDH2 mutations aid in the diagnosis of grade II and grade III astrocytomas (NCCN.org).	detail...
MAP2K1 mutant	Erdheim-Chester disease	sensitive	Trametinib	Guideline	Actionable	Mekinist (trametinib) is included in guidelines as first-line or subsequent-line therapy for patients with Erdheim-Chester disease harboring mutations in the MAPK pathway such as ARAF, NRAS, KRAS, MAP2K1/2, PIK3CA, or with no detectable mutations, or for whom testing is not available (NCCN.org).	detail...
BRAF V600K	skin melanoma	sensitive	Vemurafenib	Guideline	Actionable	Zelboraf (vemurafenib) therapy is included in guidelines for cutaneous melanoma patients with unresectable or metastatic disease harboring BRAF V600 activating mutations, such as BRAF V600K, in cases where BRAF/MEK inhibitor combination therapy is contraindicated (NCCN.org).	detail...
MSH6 negative	appendix adenocarcinoma	sensitive	Ipilimumab + Nivolumab	Guideline	Actionable	Opdivo (nivolumab) in combination with Yervoy (ipilimumab) is included in guidelines (category 2A) for patients with advanced or metastatic appendiceal adenocarcinoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
MSH6 negative	small intestine adenocarcinoma	sensitive	Avelumab	Guideline	Actionable	Bavencio (avelumab) is included in guidelines as systemic therapy (category 2A) for patients with advanced or metastatic small bowel adenocarcinoma with deficient mismatch repair (dMMR, often defined by the loss of MSH6, MSH2, PMS2, or MLH1 expression by IHC) (NCCN.org).	detail...
TP53 mutant	medulloblastoma	not applicable	N/A	Guideline	Prognostic	TP53 mutations are associated with aggressive disease in patients with SHH-activated medulloblastoma (NCCN.org).	detail...
FLT3 exon 14 ins	acute myeloid leukemia	sensitive	Azacitidine + Sorafenib	Guideline	Actionable	Nexavar (sorafenib) in combination with Vidaza (azacitidine) is included in guidelines for patients with relapsed or refractory acute myeloid leukemia harboring a FLT3 internal tandem duplication (FLT3-ITD) mutation (NCCN.org).	detail...
MLH1 negative	stomach cancer	sensitive	Fluorouracil + Oxaliplatin + Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab), in combination with Adrucil (fluorouracil) and Eloxatin (oxaliplatin) is included in guidelines as first-line therapy for patients with unresectable locally advanced, recurrent, or metastatic gastric cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
IDH2 mutant	oligodendroglioma	not applicable	N/A	Guideline	Diagnostic	IDH2 mutations aid in the diagnosis of oligodendrogliomas (NCCN.org).	detail...
ALK rearrange	lung non-small cell carcinoma	sensitive	Alectinib	Guideline	Actionable	Alecensa (alectinib) is included in guidelines as perioperative systemic therapy (category 1) for patients with ALK-rearranged advanced or metastatic non-small cell lung cancer, and as preferred first-line therapy (category 1) and as subsequent therapy for patients with advanced or metastatic disease (NCCN.org).	detail...
NRAS G13X	myelodysplastic syndrome	not applicable	N/A	Guideline	Prognostic	NRAS G13X is associated with a poor prognosis in patients with myelodysplastic syndrome (NCCN.org).	detail...
BRAF V600E	rectum cancer	sensitive	Cetuximab + Encorafenib + Fluorouracil + Leucovorin + Oxaliplatin	Guideline	Actionable	Braftovi (encorafenib) in combination with Erbitux (cetuximab) and FOLFOX is included in guidelines as a preferred initial therapy (category 2A) for patients with advanced or metastatic rectal cancer harboring BRAF V600E (NCCN.org).	detail...
NTRK1 fusion	intrahepatic cholangiocarcinoma	sensitive	Repotrectinib	Guideline	Actionable	Augtyro (repotrectinib) is included in guidelines as primary and subsequent-line therapy (category 2A) for patients with unresectable or metastatic biliary tract cancer harboring NTRK fusions, including intrahepatic cholangiocarcinoma (NCCN.org).	detail...
FLT3 exon22	acute myeloid leukemia	sensitive	Cytarabine + Midostaurin	Guideline	Actionable	Rydapt (midostaurin) in combination with Cytosar-U (cytarabine) is included in guidelines as consolidation therapy for patients with acute myeloid leukemia harboring a mutation in the FLT3 tyrosine kinase domain (exons 14-23) (NCCN.org).	detail...
RET inact mut	pheochromocytoma	not applicable	N/A	Guideline	Risk Factor	Germline pathogenic RET mutations result in multiple endocrine neoplasia type 2 (MEN2), which is associated with increased risk of developing pheochromocytoma (NCCN.org).	detail...
ROS1 rearrange	lung non-small cell carcinoma	sensitive	Entrectinib	Guideline	Actionable	Rozlytrek (entrectinib) is included in guidelines as a first-line or subsequent therapy for patients with advanced or metastatic ROS1 rearrangement-positive non-small cell lung cancer (NCCN.org).	detail...
NTRK1 fusion	oncocytic carcinoma of the thyroid	sensitive	Entrectinib	Guideline	Actionable	Rozlytrek (entrectinib) is included in guidelines for patients with RAI-refractory oncocytic thyroid carcinoma harboring an NTRK fusion with progressive or symptomatic disease (NCCN.org).	detail...
NTRK1 fusion	vulva squamous cell carcinoma	sensitive	Repotrectinib	Guideline	Actionable	Augtyro (repotrectinib) is included in guidelines as a second-line or subsequent therapy for patients with advanced or recurrent/metastatic vulvar squamous cell carcinoma harboring an NTRK fusion (NCCN.org).	detail...
FLT3 exon 14 ins	acute myeloid leukemia	sensitive	Decitabine + Sorafenib	Guideline	Actionable	Nexavar (sorafenib) in combination with Dacogen (decitabine) is included in guidelines for patients with relapsed or refractory acute myeloid leukemia harboring a FLT3 internal tandem duplication (FLT3-ITD) mutation (NCCN.org).	detail...
CTNNB1 mutant	medulloblastoma	not applicable	N/A	Guideline	Prognostic	WNT-driven medulloblastomas, characterized by CTNNB1 or APC mutations, are associated with favorable prognosis (NCCN.org).	detail...
RET fusion	follicular thyroid carcinoma	sensitive	Pralsetinib	Guideline	Actionable	Gavreto (pralsetinib) is included in guidelines for patients with RAI-refractory follicular thyroid carcinoma harboring a RET fusion with progressive or symptomatic disease (NCCN.org).	detail...
RET fusion	vaginal carcinoma	sensitive	Selpercatinib	Guideline	Actionable	Retevmo (selpercatinib) is included in guidelines as second-line or subsequent therapy for patients with recurrent or metastatic vaginal squamous cell carcinoma or adenocarcinoma harboring an RET fusion (NCCN.org).	detail...
NTRK1 fusion	salivary gland cancer	sensitive	Entrectinib	Guideline	Actionable	Rozlytrek (entrectinib) is included in guidelines for patients with NTRK1 fusion-positive salivary gland tumors with distant metastasis (NCCN.org).	detail...
MLH1 negative	gastroesophageal junction adenocarcinoma	sensitive	Dostarlimab-gxly	Guideline	Actionable	Jemperli (dostarlimab-gxly) is included in guidelines as neoadjuvant, preferred first-line, second-line, or subsequent therapy for patients with unresectable locally advanced, recurrent, or metastatic gastroesophageal junction adenocarcinoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
NTRK2 fusion	small intestine adenocarcinoma	sensitive	Repotrectinib	Guideline	Actionable	Augtyro (repotrectinib) is included in guidelines as second-line or subsequent therapy (category 2A) for patients with advanced or metastatic small bowel adenocarcinoma harboring an NTRK fusion (NCCN.org).	detail...
RET fusion	extrahepatic bile duct carcinoma	sensitive	Selpercatinib	Guideline	Actionable	Retevmo (selpercatinib) is included in guidelines as primary (category 2B) and subsequent-line therapy for patients with unresectable or metastatic biliary tract cancer harboring RET fusions, including extrahepatic cholangiocarcinoma (NCCN.org).	detail...
FGFR1 fusion	glottis cancer	sensitive	Erdafitinib	Guideline	Actionable	Balversa (erdafitinib) is included in guidelines as subsequent-line therapy (category 2B) for patients with glottic larynx cancer harboring FGFR mutations or fusions and with no alternative options (NCCN.org).	detail...
FLT3 exon19	acute myeloid leukemia	sensitive	Cytarabine + Daunorubicin + Midostaurin	Guideline	Actionable	Rydapt (midostaurin), in combination with Cerubidine (daunorubicin) and Cytosar-U (cytarabine), is included in guidelines for patients with acute myeloid leukemia harboring a mutation in the FLT3 tyrosine kinase domain (exons 14-23) (NCCN.org).	detail...
NTRK2 fusion	papillary thyroid carcinoma	sensitive	Repotrectinib	Guideline	Actionable	Augtyro (repotrectinib) is included in guidelines for patients with RAI-refractory papillary thyroid carcinoma harboring an NTRK fusion with progressive or symptomatic disease (NCCN.org).	detail...
NTRK2 fusion	uterine corpus sarcoma	sensitive	Repotrectinib	Guideline	Actionable	Augtyro (repotrectinib) is included in guidelines as first-line therapy for patients with advanced, recurrent, metastatic, or inoperable uterine sarcoma harboring an NTRK fusion (NCCN.org).	detail...
KIT D816V	systemic mastocytosis	not applicable	N/A	Guideline	Diagnostic	KIT D816V aids in the diagnosis of systemic mastocytosis (NCCN.org).	detail...
MSH6 negative	small intestine adenocarcinoma	sensitive	Atezolizumab	Guideline	Actionable	Tecentriq (atezolizumab) is included in guidelines as systemic therapy (category 2A) for patients with advanced or metastatic small bowel adenocarcinoma with deficient mismatch repair (dMMR, often defined by the loss of MSH6, MSH2, PMS2, or MLH1 expression by IHC) (NCCN.org).	detail...
MLH1 negative	supraglottis cancer	sensitive	Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab) is included in guidelines as first- and subsequent-line therapy for patients with mismatch repair deficient (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) recurrent, unresectable, or metastatic supraglottic larynx cancer (NCCN.org).	detail...
BRAF V600E	papillary thyroid carcinoma	sensitive	Dabrafenib + Trametinib	Guideline	Actionable	The combination of Tafinlar (dabrafenib) and Mekinist (trametinib) is included in guidelines for patients with RAI-refractory papillary thyroid carcinoma harboring BRAF V600E who have progressed on therapy and have no further treatment options (NCCN.org).	detail...
MSH6 negative	appendix adenocarcinoma	sensitive	Nivolumab	Guideline	Actionable	Opdivo (nivolumab) is included in guidelines (category 2A) for patients with advanced or metastatic appendiceal adenocarcinoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
FGFR3 fusion	glottis cancer	sensitive	Erdafitinib	Guideline	Actionable	Balversa (erdafitinib) is included in guidelines as subsequent-line therapy (category 2B) for patients with glottic larynx cancer harboring FGFR mutations or fusions and with no alternative options (NCCN.org).	detail...
FGFR3 act mut	maxillary sinus cancer	sensitive	Erdafitinib	Guideline	Actionable	Balversa (erdafitinib) is included in guidelines as subsequent-line therapy (category 2B) for patients with maxillary sinus cancer harboring FGFR mutations or fusions and with no alternative options (NCCN.org).	detail...
NTRK2 fusion	lung non-small cell carcinoma	sensitive	Repotrectinib	Guideline	Actionable	Augtyro (repotrectinib) is included in guidelines as first-line or subsequent therapy for patients with advanced or metastatic non-small cell lung cancer harboring an NTRK2 fusion (NCCN.org).	detail...
FLT3 exon19	acute myeloid leukemia	sensitive	Gilteritinib	Guideline	Actionable	Xospata (gilteritinib) is included in guidelines for patients with relapsed or refractory acute myeloid leukemia harboring a mutation in the FLT3 tyrosine kinase domain (exons 14-23) (NCCN.org).	detail...
ABL1 rearrange	childhood B-cell acute lymphoblastic leukemia	not applicable	N/A	Guideline	Prognostic	ABL1 rearrangements are associated with a poor prognosis in pediatric patients with B-cell acute lymphoblastic leukemia (NCCN.org).	detail...
MSH6 negative	supraglottis cancer	sensitive	Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab) is included in guidelines as first- and subsequent-line therapy for patients with mismatch repair deficient (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) recurrent, unresectable, or metastatic supraglottic larynx cancer (NCCN.org).	detail...
RET C620X	medullary thyroid carcinoma	not applicable	N/A	Guideline	Risk Factor	Germline RET C620X mutations result in multiple endocrine neoplasia, type 2A (MEN 2A), which is associated with high risk of developing thyroid medullary carcinoma (NCCN.org).	detail...
NTRK1 fusion	Adenocarcinoma of Unknown Primary	sensitive	Entrectinib	Guideline	Actionable	Rozlytrek (entrectinib) is included in guidelines for patients with adenocarcinoma of unknown primary harboring NTRK1 fusions (NCCN.org).	detail...
FLT3 exon17	acute myeloid leukemia	sensitive	Cytarabine + Daunorubicin + Midostaurin	Guideline	Actionable	Rydapt (midostaurin), in combination with Cerubidine (daunorubicin) and Cytosar-U (cytarabine), is included in guidelines for patients with acute myeloid leukemia harboring a mutation in the FLT3 tyrosine kinase domain (exons 14-23) (NCCN.org).	detail...
IDH1 wild-type	high grade glioma	not applicable	N/A	Guideline	Risk Factor	IDH1 wild-type is associated with increased risk of aggressive disease in patients with grade II or III infiltrative gliomas (NCCN.org).	detail...
NTRK1 fusion	anaplastic oligodendroglioma	sensitive	Larotrectinib	Guideline	Actionable	Vitrakvi (larotrectinib) is included in guidelines for patients with recurrent anaplastic gliomas harboring an NTRK fusion, including anaplastic oligodendroglioma (NCCN.org).	detail...
NTRK1 fusion	colon cancer	sensitive	Entrectinib	Guideline	Actionable	Rozlytrek (entrectinib) is included in guidelines for advanced or metastatic colon cancer patients with an NTRK fusion (NCCN.org).	detail...
BRAF V600X	pleomorphic xanthoastrocytoma	sensitive	Tovorafenib	Guideline	Actionable	Ojemda (tovorafenib) is included in guidelines (category 2A) for patients with recurrent or progressive circumscribed glioma, including pleomorphic xanthoastrocytoma, harboring BRAF fusions, rearrangements, or BRAF V600 mutations (NCCN.org).	detail...
MSH6 negative	esophagus adenocarcinoma	sensitive	Fluorouracil + Oxaliplatin + Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab), in combination with Adrucil (fluorouracil) and Eloxatin (oxaliplatin) is included in guidelines as first-line therapy for patients with unresectable locally advanced, recurrent, or metastatic esophageal adenocarcinoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
PIK3CA exon21	colon cancer	sensitive	Aspirin	Guideline	Actionable	Aspirin is included in guidelines as adjuvant therapy (category 2A) for patients with advanced colon cancer harboring PIK3CA exon 21 (reported as exon 20) mutations, including hotspot mutations occurring at Y1021, M1043, N1044, and H1047, and other somatic mutations affecting the PI3K pathway genes PIK3CA, PIK3R1, or PTEN (NCCN.org).	detail...
MLH1 negative	gastroesophageal junction adenocarcinoma	sensitive	Capecitabine + Oxaliplatin + Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab), in combination with Xeloda (capecitabine) and Eloxatin (oxaliplatin) is included in guidelines as first-line therapy for patients with unresectable locally advanced, recurrent, or metastatic gastroesophageal junction adenocarcinoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
RET fusion	soft tissue sarcoma	sensitive	Selpercatinib	Guideline	Actionable	Retevmo (selpercatinib) is included in guidelines as first-line therapy for patients with advanced or metastatic soft tissue sarcoma harboring RET fusions (NCCN.org).	detail...
NTRK2 fusion	Erdheim-Chester disease	sensitive	Entrectinib	Guideline	Actionable	Rozlytrek (entrectinib) is included in guidelines as first-line or subsequent-line therapy for patients with Erdheim-Chester disease harboring NTRK2 fusions (NCCN.org).	detail...
NRAS mutant	myelofibrosis	not applicable	N/A	Guideline	Prognostic	NRAS mutations are associated with decreased overall survival in patients with primary myelofibrosis (NCCN.org).	detail...
MSH6 negative	gastroesophageal junction adenocarcinoma	sensitive	Capecitabine + Oxaliplatin + Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab), in combination with Xeloda (capecitabine) and Eloxatin (oxaliplatin) is included in guidelines as first-line therapy for patients with unresectable locally advanced, recurrent, or metastatic gastroesophageal junction adenocarcinoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
NTRK1 fusion	appendix adenocarcinoma	sensitive	Entrectinib	Guideline	Actionable	Rozlytrek (entrectinib) is included in guidelines (category 2A) as second-line or subsequent therapy for patients with advanced or metastatic appendiceal adenocarcinoma harboring an NTRK fusion (NCCN.org).	detail...
NTRK2 fusion	stomach cancer	sensitive	Entrectinib	Guideline	Actionable	Rozlytrek (entrectinib) is included in guidelines as second-line or subsequent therapy for patients with unresectable locally advanced, recurrent, or metastatic gastric cancer harboring an NTRK2 fusion (NCCN.org).	detail...
MLH1 negative	gastroesophageal junction adenocarcinoma	sensitive	Durvalumab + Tremelimumab	Guideline	Actionable	Imfinzi (durvalumab), in combination with Imjudo (tremelimumab), is included in guidelines as neoadjuvant therapy for patients with gastroesophageal junction adenocarcinoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
BRAF V600E/K	skin melanoma	sensitive	Vemurafenib	Guideline	Actionable	Zelboraf (vemurafenib) therapy is included in cutaneous melanoma guidelines for patients with metastatic or unresectable disease harboring a BRAF V600 activating mutation (NCCN.org).	detail...
MLH1 negative	stomach cancer	sensitive	Dostarlimab-gxly	Guideline	Actionable	Jemperli (dostarlimab-gxly) is included in guidelines as first-line, second-line, or subsequent therapy for patients with unresectable locally advanced or metastatic gastric cancer with deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
MLH1 negative	esophagus adenocarcinoma	sensitive	Capecitabine + Oxaliplatin + Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab), in combination with Xeloda (capecitabine) and Eloxatin (oxaliplatin) is included in guidelines as first-line therapy for patients with unresectable locally advanced, recurrent, or metastatic esophageal adenocarcinoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
RET E768X	medullary thyroid carcinoma	not applicable	N/A	Guideline	Risk Factor	Germline RET E768X mutations result in multiple endocrine neoplasia, type 2A (MEN 2A), which is associated with increased risk of developing thyroid medullary carcinoma (NCCN.org).	detail...
RET V804M RET Y806C	medullary thyroid carcinoma	not applicable	N/A	Guideline	Risk Factor	Compound germline RET V804M and Y806C mutations result in multiple endocrine neoplasia, type 2B (MEN 2B), which is associated with high risk of developing thyroid medullary carcinoma (NCCN.org).	detail...
KIT act mut	skin melanoma	sensitive	Nilotinib	Guideline	Actionable	Tasigna (nilotinib) is included in guidelines as second-line therapy for metastatic or unresectable cutaneous melanoma patients with KIT activating mutations (NCCN.org).	detail...
NTRK2 fusion	anaplastic oligodendroglioma	sensitive	Entrectinib	Guideline	Actionable	Rozlytrek (entrectinib) is included in guidelines for patients with recurrent anaplastic gliomas harboring an NTRK fusion, including anaplastic oligodendroglioma (NCCN.org).	detail...
NTRK2 fusion	stomach cancer	sensitive	Repotrectinib	Guideline	Actionable	Augtyro (repotrectinib) is included in guidelines as second-line or subsequent therapy for patients with unresectable locally advanced, recurrent, or metastatic gastric cancer harboring an NTRK2 fusion (NCCN.org).	detail...
IDH1 wild-type	IDH-wildtype glioblastoma	not applicable	N/A	Guideline	Diagnostic	Wild-type IDH1 aids in the diagnosis of glioblastoma (NCCN.org).	detail...
BRAF mutant	splenic marginal zone lymphoma	not applicable	N/A	Guideline	Diagnostic	BRAF mutations aid in the diagnosis of splenic marginal zone lymphoma (NCCN.org).	detail...
ALK rearrange	lung non-small cell carcinoma	sensitive	Ceritinib	Guideline	Actionable	Zykadia (ceritinib) is included in guidelines as first-line (category 1) and as subsequent therapy for patients with advanced or metastatic ALK-rearranged non-small cell lung cancer (NCCN.org).	detail...
ALK rearrange	lung non-small cell carcinoma	no benefit	Atezolizumab	Guideline	Actionable	Monotherapy with immune checkpoint inhibitors, including Opdivo (nivolumab), Keytruda (pembrolizumab), Tecentriq (atezolizumab), and Imfinzi (durvalumab), is not indicated for use as initial systemic therapy or subsequent therapy in non-small cell lung cancer patients harboring oncogenic drivers, including ALK rearrangement (NCCN.org).	detail...
JAK3 rearrange	B-cell acute lymphoblastic leukemia	not applicable	N/A	Guideline	Prognostic	JAK3 rearrangements are associated with a poor prognosis in patients with B-cell acute lymphoblastic leukemia (NCCN.org).	detail...
MSH6 negative	ampulla of Vater adenocarcinoma	sensitive	Nivolumab	Guideline	Actionable	Opdivo (nivolumab) is included in guidelines as first-line therapy (category 2A) for metastatic ampullary adenocarcinoma patients with deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) and poor (ECOG 3) performance status, and as subsequent therapy (category 2A) for patients with intermediate (ECOG 2) or poor (ECOG 3) performance status (NCCN.org).	detail...
RET rearrange	lung non-small cell carcinoma	sensitive	Selpercatinib	Guideline	Actionable	Retevmo (selpercatinib) is in guidelines as a first-line therapy (category 1) for patients with advanced or metastatic non-small cell lung cancer harboring RET rearrangements (NCCN.org).	detail...
FLT3 rearrange	myeloid neoplasm	sensitive	Midostaurin	Guideline	Actionable	Rydapt (midostaurin) is included in guidelines for patients with a myeloid/lymphoid neoplasm with eosinophilia harboring a FLT3 rearrangement (NCCN.org).	detail...
NTRK1 fusion	follicular thyroid carcinoma	sensitive	Repotrectinib	Guideline	Actionable	Augtyro (repotrectinib) is included in guidelines for patients with RAI-refractory oncocytic thyroid carcinoma harboring an NTRK fusion with progressive or symptomatic disease (NCCN.org).	detail...
NTRK2 fusion	ampulla of Vater adenocarcinoma	sensitive	Larotrectinib	Guideline	Actionable	Vitrakvi (larotrectinib) is included in guidelines as first-line or subsequent therapy for patients with metastatic ampullary adenocarcinoma harboring NTRK fusions (NCCN.org).	detail...
JAK2 mutant	myelofibrosis	not applicable	N/A	Guideline	Diagnostic	JAK2 mutations aid in the diagnosis of primary myelofibrosis (NCCN.org).	detail...
MSH6 negative	hypopharynx cancer	sensitive	Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab) is included in guidelines as first- and subsequent-line therapy for patients with mismatch repair deficient (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) recurrent, unresectable, or metastatic hypopharynx cancer (NCCN.org).	detail...
MLH1 negative	esophagus adenocarcinoma	sensitive	Ipilimumab + Nivolumab	Guideline	Actionable	Opdivo (nivolumab), in combination with Yervoy (ipilimumab), is included in guidelines as first-line, second-line, or subsequent therapy for patients with unresectable locally advanced, recurrent, or metastatic esophageal adenocarcinoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
NTRK2 fusion	vulva adenocarcinoma	sensitive	Repotrectinib	Guideline	Actionable	Augtyro (repotrectinib) is included in guidelines as a second-line or subsequent therapy for patients with advanced or recurrent/metastatic vulvar adenocarcinoma harboring an NTRK fusion (NCCN.org).	detail...
BRAF V600E	papillary thyroid carcinoma	sensitive	Dabrafenib	Guideline	Actionable	Tafinlar (dabrafenib) is included in guidelines for patients with RAI-refractory papillary thyroid carcinoma harboring BRAF V600E for whom clinical trials or other systemic therapies are not available or appropriate (category 2B) (NCCN.org).	detail...
FLT3 exon 15 ins	acute myeloid leukemia	sensitive	Cytarabine + Midostaurin	Guideline	Actionable	Rydapt (midostaurin) in combination with Cytosar-U (cytarabine) is included in guidelines as consolidation therapy for patients with acute myeloid leukemia harboring a FLT3 internal tandem duplication (FLT3-ITD) mutation (NCCN.org).	detail...
NTRK1 fusion	extrahepatic bile duct carcinoma	sensitive	Larotrectinib	Guideline	Actionable	Vitrakvi (larotrectinib) is included in guidelines as primary and subsequent-line therapy for patients with unresectable or metastatic biliary tract cancer harboring an NTRK fusion, including extrahepatic cholangiocarcinoma (NCCN.org).	detail...
NTRK2 fusion	vulva squamous cell carcinoma	sensitive	Larotrectinib	Guideline	Actionable	Vitrakvi (larotrectinib) is included in guidelines as a second-line or subsequent therapy for patients with advanced or recurrent/metastatic vulvar squamous cell carcinoma harboring an NTRK fusion (NCCN.org).	detail...
MSH6 mutant	ovarian cancer	not applicable	N/A	Guideline	Risk Factor	Germline mutations in MSH6 result in Lynch syndrome, which is associated with increased risk of ovarian cancer (NCCN.org).	detail...
MLH1 negative	ovarian germ cell cancer	sensitive	Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab) is included in guidelines as recurrence therapy for patients with malignant ovarian germ cell tumors with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
NRAS exon3	rectum cancer	resistant	Cetuximab	Guideline	Actionable	Erbitux (cetuximab) is not indicated for use in rectum cancer patients with NRAS exon 3 mutations (NCCN.org).	detail...
TP53 loss	chronic lymphocytic leukemia/small lymphocytic lymphoma	sensitive	Venetoclax	Guideline	Actionable	Venclexta (venetoclax) is included in guidelines as second-line or subsequent therapy for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with TP53 loss (NCCN.org).	detail...
FLT3 exon23	acute myeloid leukemia	sensitive	Cytarabine + Idarubicin + Midostaurin	Guideline	Actionable	Rydapt (midostaurin) in combination with Idarubicin and Cytosar-U (cytarabine) is included in guidelines for patients with acute myeloid leukemia harboring a mutation in the FLT3 tyrosine kinase domain (exons 14-23) (NCCN.org).	detail...
KMT2A rearrange	T-cell acute lymphoblastic leukemia	sensitive	Revumenib	Guideline	Actionable	Revuforj (revumenib) is included in guidelines for patients with relapsed or refractory T-cell acute lymphoblastic leukemia harboring a KMT2A rearrangement (NCCN.org).	detail...
NTRK1 fusion	ovary epithelial cancer	sensitive	Larotrectinib	Guideline	Actionable	Vitrakvi (larotrectinib) is included in guidelines as systemic therapy for patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer harboring an NTRK fusion (NCCN.org).	detail...
BRAF V600E	small intestine adenocarcinoma	sensitive	Encorafenib + Fluorouracil + Leucovorin + Oxaliplatin + Panitumumab	Guideline	Actionable	Braftovi (encorafenib) in combination with Vectibix (panitumumab) and FOLFOX is included in guidelines as initial or subsequent-line therapy (category 2A) for patients with advanced or metastatic small bowel adenocarcinoma harboring BRAF V600E (NCCN.org).	detail...
MSH6 negative	breast cancer	sensitive	Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab) is included in guidelines for patients with recurrent unresectable or stage IV (M1) breast cancer with deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
ATM inact mut	prostate cancer	sensitive	Olaparib	Guideline	Actionable	Lynparza (olaparib) is included in guidelines as second-line therapy post androgen receptor-directed therapy for patients with metastatic castration-resistant prostate cancer harboring pathogenic mutations in ATM (NCCN.org).	detail...
RET fusion	intrahepatic cholangiocarcinoma	sensitive	Selpercatinib	Guideline	Actionable	Retevmo (selpercatinib) is included in guidelines as primary (category 2B) and subsequent-line therapy for patients with unresectable or metastatic biliary tract cancer harboring RET fusions, including intrahepatic cholangiocarcinoma (NCCN.org).	detail...
NTRK2 fusion	esophagus adenocarcinoma	sensitive	Larotrectinib	Guideline	Actionable	Vitrakvi (larotrectinib) is included in guidelines as second-line or subsequent therapy for patients with unresectable locally advanced, recurrent, or metastatic esophageal adenocarcinoma with an NTRK fusion (NCCN.org).	detail...
NRAS exon2	rectum cancer	resistant	Cetuximab	Guideline	Actionable	Erbitux (cetuximab) is not indicated for use in rectum cancer patients with NRAS exon 2 mutations (NCCN.org).	detail...
NTRK1 fusion	neuroendocrine tumor	sensitive	Repotrectinib	Guideline	Actionable	Augtyro (repotrectinib) is included in guidelines for patients with unresectable or metastatic extrapulmonary poorly differentiated neuroendocrine carcinoma, large or small cell carcinoma, or mixed neuroendocrine/non-neuroendocrine neoplasms harboring an NTRK fusion who have progressed on a prior NTRK-targeted therapy (NCCN.org).	detail...
NTRK1 fusion	uterine corpus sarcoma	sensitive	Entrectinib	Guideline	Actionable	Rozlytrek (entrectinib) is included in guidelines as first-line therapy for patients with advanced, recurrent, metastatic, or inoperable uterine sarcoma harboring an NTRK fusion (NCCN.org).	detail...
TP53 mutant	chronic lymphocytic leukemia/small lymphocytic lymphoma	not applicable	N/A	Guideline	Prognostic	TP53 mutations are associated with a poor prognosis in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (NCCN.org).	detail...
BRAF V600X	skin melanoma	sensitive	Vemurafenib	Guideline	Actionable	Zelboraf (vemurafenib) therapy is included in guidelines for patients with unresectable or metastatic cutaneous melanoma harboring BRAF V600 activating mutations, in cases where BRAF/MEK inhibitor combination therapy is contraindicated (NCCN.org).	detail...
PIK3CA exon10	rectum cancer	sensitive	Aspirin	Guideline	Actionable	Aspirin is included in guidelines as adjuvant therapy (category 2A) for patients with advanced rectal cancer harboring PIK3CA exon 10 (reported as exon 9) mutations, including hotspot mutations occurring at E542, E545, and Q546, and other somatic mutations affecting the PI3K pathway genes PIK3CA, PIK3R1, or PTEN (NCCN.org).	detail...
FLT3 exon22	acute myeloid leukemia	sensitive	Gilteritinib	Guideline	Actionable	Xospata (gilteritinib) is included in guidelines for patients with relapsed or refractory acute myeloid leukemia harboring a mutation in the FLT3 tyrosine kinase domain (exons 14-23) (NCCN.org).	detail...
ALK rearrange	lung non-small cell carcinoma	sensitive	Lorlatinib	Guideline	Actionable	Lorbrena (lorlatinib) is included in guidelines as preferred first-line therapy (category 1) and as subsequent therapy for patients with advanced or metastatic ALK-rearranged non-small cell lung cancer (NCCN.org).	detail...
RET fusion	cholangiocarcinoma	sensitive	Selpercatinib	Guideline	Actionable	Retevmo (selpercatinib) is included in guidelines as primary (category 2B) or subsequent-line therapy (category 2A) for patients with unresectable or metastatic cholangiocarcinoma harboring RET fusions (NCCN.org).	detail...
NTRK1 fusion	lung non-small cell carcinoma	sensitive	Larotrectinib	Guideline	Actionable	Vitrakvi (larotrectinib) is included in guidelines as first-line or subsequent therapy for patients with advanced or metastatic non-small cell lung cancer harboring an NTRK1 fusion (NCCN.org).	detail...
MSH6 negative	endometrial carcinoma	sensitive	Dostarlimab-gxly	Guideline	Actionable	Jemperli (dostarlimab-gxly) is included in guidelines as first-line or second-line therapy for patients with high microsatellite instability (MSI-H) or mismatch repair deficient (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) recurrent endometrial carcinoma (NCCN.org).	detail...
BRAF fusion	subependymal giant cell astrocytoma	sensitive	Tovorafenib	Guideline	Actionable	Ojemda (tovorafenib) is included in guidelines (category 2A) for patients with recurrent or progressive circumscribed glioma, including subependymal giant cell astrocytoma, harboring BRAF fusions, rearrangements, or BRAF V600 mutations (NCCN.org).	detail...
MLH1 negative	endometrial carcinoma	sensitive	Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab) is included in guidelines as first-line or subsequent-line therapy for patients with recurrent or metastatic endometrial carcinoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
ATM mutant	skin melanoma	not applicable	N/A	Guideline	Risk Factor	Germline ATM mutations or polymorphisms are associated with increased risk of developing single or multiple primary cutaneous melanomas (NCCN.org).	detail...
ALK rearrange	lung non-small cell carcinoma	no benefit	Pembrolizumab	Guideline	Actionable	Monotherapy with immune checkpoint inhibitors, including Opdivo (nivolumab), Keytruda (pembrolizumab), Tecentriq (atezolizumab), and Imfinzi (durvalumab), is not indicated for use as initial systemic therapy or subsequent therapy in non-small cell lung cancer patients harboring oncogenic drivers, including ALK rearrangement (NCCN.org).	detail...
ALK rearrange ALK L1196M ALK G1202R	lung non-small cell carcinoma	resistant	Lorlatinib	Guideline	Actionable	Lorbrena (lorlatinib) is not indicated for use as subsequent therapy for patients with advanced or metastatic ALK-rearranged non-small cell lung cancer harboring ALK L1196M and G1202R compound mutations (NCCN.org).	detail...
MSH6 negative	endometrial carcinoma	sensitive	Avelumab	Guideline	Actionable	Bavencio (avelumab) is included in guidelines as a second-line or subsequent-line therapy for patients with high microsatellite instability (MSI-H) or mismatch repair deficient (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) recurrent endometrial carcinoma (NCCN.org).	detail...
NTRK2 fusion	pancreatic adenocarcinoma	sensitive	Entrectinib	Guideline	Actionable	Rozlytrek (entrectinib) is included in guidelines as first-line therapy for pancreatic adenocarcinoma patients harboring an NTRK fusion with locally advanced disease with good (ECOG 0-1) or intermediate (ECOG 2) performance status (PS), as first-line therapy for patients with metastatic disease with good, intermediate (category 2A), or poor (ECOG 3) (category 2B) PS, as subsequent therapy for patients with locally advanced, metastatic, or recurrent disease (NCCN.org).	detail...
NTRK1 fusion	gastroesophageal junction adenocarcinoma	sensitive	Entrectinib	Guideline	Actionable	Rozlytrek (entrectinib) is included in guidelines as second-line or subsequent therapy for patients with unresectable locally advanced, recurrent, or metastatic gastroesophageal junction adenocarcinoma with an NTRK fusion (NCCN.org).	detail...
BRAF V600E	rectum cancer	sensitive	Cetuximab + Encorafenib + Fluorouracil + Irinotecan + Leucovorin	Guideline	Actionable	Braftovi (encorafenib) in combination with Erbitux (cetuximab) and FOLFIRI is included in guidelines as a preferred initial therapy (category 2A) for patients with advanced or metastatic rectal cancer harboring BRAF V600E (NCCN.org).	detail...
NRAS wild-type	rectum cancer	predicted - sensitive	Panitumumab	Guideline	Actionable	Vecitbix (panitumumab), alone and in combination with chemotherapy, is included in guidelines for patients with advanced or metastatic rectal cancer that is BRAF wild-type, KRAS wild-type, and NRAS wild-type (NCCN.org).	detail...
MSH6 negative	colon cancer	sensitive	Toripalimab-tpzi	Guideline	Actionable	Loqtorz (toripalimab-tpzi) is included in guidelines (category 2A) for patients with advanced or metastatic colon cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, MSH2, PMS2, or MSH6 expression by IHC) (NCCN.org).	detail...
MLH1 negative	endometrial carcinoma	sensitive	Retifanlimab	Guideline	Actionable	Zynyz (retifanlimab) is included in guidelines as a second-line or subsequent-line therapy (category 2B) for patients with high microsatellite instability (MSI-H) or mismatch repair-deficient (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) recurrent endometrial carcinoma (NCCN.org).	detail...
MLH1 negative	breast cancer	sensitive	Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab) is included in guidelines for patients with recurrent unresectable or stage IV (M1) breast cancer with deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
NTRK2 fusion	rectum cancer	sensitive	Repotrectinib	Guideline	Actionable	Augtyro (repotrectinib) is included in guidelines as second-line or subsequent therapy (category 2A) for patients with advanced or metastatic rectal cancer harboring an NTRK fusion (NCCN.org).	detail...
NTRK2 fusion	salivary gland cancer	sensitive	Repotrectinib	Guideline	Actionable	Augtyro (repotrectinib) is included in guidelines for patients with unresectable locally advanced, recurrent, or metastatic salivary gland tumors harboring an NTRK2 fusion (NCCN.org).	detail...
MSH6 negative	colon cancer	sensitive	Cemiplimab	Guideline	Actionable	Libtayo (cemiplimab) is included in guidelines (category 2A) for patients with advanced or metastatic colon cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
BRAF V600E	pleomorphic xanthoastrocytoma	sensitive	Cobimetinib + Vemurafenib	Guideline	Actionable	Zelboraf (vemurafenib) and Cotellic (cobimetinib) combination therapy is included in guidelines as an adjuvant treatment for patients with pleomorphic xanthoastrocytoma harboring BRAF V600E (NCCN.org).	detail...
MSH6 negative	stomach cancer	sensitive	Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab) is included in guidelines as first-line, second-line, or subsequent therapy for patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) stomach cancer that are unresectable, locally advanced, recurrent, or metastatic (NCCN.org).	detail...
RET M918X	medullary thyroid carcinoma	not applicable	N/A	Guideline	Risk Factor	Germline RET M918X mutations result in multiple endocrine neoplasia, type 2B (MEN 2B), which is associated with high risk of developing thyroid medullary carcinoma (NCCN.org).	detail...
MSH6 negative	small intestine adenocarcinoma	sensitive	Cosibelimab	Guideline	Actionable	Unloxcyt (cosibelimab) is included in guidelines as systemic therapy (category 2A) for patients with advanced or metastatic small bowel adenocarcinoma with deficient mismatch repair (dMMR, often defined by the loss of MSH6, MSH2, PMS2, or MLH1 expression by IHC) (NCCN.org).	detail...
NTRK2 fusion	gallbladder cancer	sensitive	Larotrectinib	Guideline	Actionable	Vitrakvi (larotrectinib) is included in guidelines as primary and subsequent-line therapy for patients with unresectable or metastatic biliary tract cancer harboring an NTRK fusion, including gallbladder cancer (NCCN.org).	detail...
NTRK2 fusion	Erdheim-Chester disease	sensitive	Repotrectinib	Guideline	Actionable	Augtyro (repotrectinib) is included in guidelines as first-line or subsequent-line therapy for patients with Erdheim-Chester disease harboring NTRK2 fusions (NCCN.org).	detail...
NTRK2 fusion	anaplastic astrocytoma	sensitive	Entrectinib	Guideline	Actionable	Rozlytrek (entrectinib) is included in guidelines for patients with recurrent anaplastic gliomas harboring an NTRK fusion, including anaplastic astrocytoma (NCCN.org).	detail...
MLH1 negative	small intestine adenocarcinoma	sensitive	Atezolizumab + Fluorouracil + Leucovorin + Oxaliplatin	Guideline	Actionable	Tecentriq (atezolizumab) in combination with Adrucil (fluorouracil), Wellcovorin (leucovorin), and Eloxatin (oxaliplatin) is included in guidelines as adjuvant therapy (category 2A) for patients with small bowel adenocarcinoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, MSH2, MSH6, or PMS2 expression by IHC) (NCCN.org).	detail...
BRAF V600E	oncocytic carcinoma of the thyroid	sensitive	Vemurafenib	Guideline	Actionable	Zelboraf (vemurafenib) is included in guidelines for patients with RAI-refractory oncocytic thyroid carcinoma harboring BRAF V600E for whom clinical trials or other systemic therapies are not available or appropriate (category 2B) (NCCN.org).	detail...
IDH1 mutant	acute myeloid leukemia	sensitive	Decitabine	Guideline	Actionable	Dacogen (decitabine) is included in guidelines for adult patients with acute myeloid leukemia harboring an IDH1 mutation (NCCN.org).	detail...
NTRK2 fusion	ampulla of Vater adenocarcinoma	sensitive	Entrectinib	Guideline	Actionable	Rozlytrek (entrectinib) is included in guidelines as first-line or subsequent therapy for patients with metastatic ampullary adenocarcinoma harboring NTRK fusions (NCCN.org).	detail...
NTRK1 fusion	Adenocarcinoma of Unknown Primary	sensitive	Larotrectinib	Guideline	Actionable	Vitrakvi (larotrectinib) is included in guidelines for patients with adenocarcinoma of unknown primary harboring NTRK1 fusions (NCCN.org).	detail...
NTRK1 fusion	pilocytic astrocytoma	sensitive	Repotrectinib	Guideline	Actionable	Augtyro (repotrectinib) is included in guidelines (category 2B) for patients with recurrent or progressive circumscribed glioma, including pilocytic astrocytoma, harboring an NTRK fusion (NCCN.org).	detail...
MSH6 negative	small intestine adenocarcinoma	sensitive	Cemiplimab	Guideline	Actionable	Libtayo (cemiplimab) is included in guidelines as systemic therapy (category 2A) for patients with advanced or metastatic small bowel adenocarcinoma with deficient mismatch repair (dMMR, often defined by the loss of MSH6, MSH2, PMS2, or MLH1 expression by IHC) (NCCN.org).	detail...
IDH1 act mut	astrocytoma, IDH-mutant, grade 4	sensitive	Vorasidenib	Guideline	Actionable	Voranigo (vorasidenib) is included in guidelines for patients with recurrent or progressive (category 2B) WHO grade 4 astrocytoma harboring an IDH1 activating mutation (NCCN.org).	detail...
FGFR3 act mut	bladder urothelial carcinoma	sensitive	Erdafitinib	Guideline	Actionable	Balversa (erdafitinib) is included in guidelines (category 1 for patients who have already received platinum and a checkpoint inhibitor) as second-line or subsequent-line therapy for patients with advanced or metastatic urothelial carcinoma harboring susceptible FGFR3 alterations (NCCN.org).	detail...
FLT3 exon16	acute myeloid leukemia	sensitive	Gilteritinib	Guideline	Actionable	Xospata (gilteritinib) is included in guidelines for patients with relapsed or refractory acute myeloid leukemia harboring a mutation in the FLT3 tyrosine kinase domain (exons 14-23) (NCCN.org).	detail...
NRAS exon3	colon cancer	resistant	Panitumumab	Guideline	Actionable	Vectibix (panitumumab) is not indicated for use in colon cancer patients with NRAS exon 3 mutations (NCCN.org).	detail...
FLT3 exon 15 ins	acute myeloid leukemia	sensitive	Gilteritinib	Guideline	Actionable	Xospata (gilteritinib) is included in the guidelines for patients with relapsed or refractory acute myeloid leukemia harboring a FLT3 internal tandem duplication (FLT3-ITD) mutation (NCCN.org).	detail...
NTRK2 fusion	esophagus squamous cell carcinoma	sensitive	Entrectinib	Guideline	Actionable	Rozlytrek (entrectinib) is included in guidelines as second-line or subsequent therapy for patients with unresectable locally advanced, recurrent, or metastatic esophageal squamous cell carcinoma with an NTRK fusion (NCCN.org).	detail...
BRAF V600E	low grade glioma	sensitive	Cobimetinib + Vemurafenib	Guideline	Actionable	Combination of Zelboraf (vemurafenib) and Cotellic (cobimetinib) is included in guidelines for patients with recurrent or progressive low grade glioma harboring BRAF V600E (NCCN.org).	detail...
BRAF V600E	lung non-small cell carcinoma	sensitive	Dabrafenib + Trametinib	Guideline	Actionable	Combination of Mekinist (trametinib) and Tafinlar (dabrafenib) is included in guidelines as a first-line or subsequent therapy for advanced or metastatic non-small cell lung cancer patients harboring BRAF V600E mutations (NCCN.org).	detail...
FLT3 exon 14 ins	acute myeloid leukemia	sensitive	Cytarabine + Daunorubicin + Midostaurin	Guideline	Actionable	Rydapt (midostaurin) in combination with Cerubidine (daunorubicin) and Cytosar-U (cytarabine) is included in guidelines for patients with acute myeloid leukemia harboring a FLT3 internal tandem duplication (FLT3-ITD) mutation (NCCN.org).	detail...
NTRK2 fusion	gastroesophageal junction adenocarcinoma	sensitive	Larotrectinib	Guideline	Actionable	Vitrakvi (larotrectinib) is included in guidelines as second-line or subsequent therapy for patients with unresectable locally advanced, recurrent, or metastatic gastroesophageal junction adenocarcinoma with an NTRK fusion (NCCN.org).	detail...
FLT3 mutant	acute myeloid leukemia	sensitive	Cytarabine + Venetoclax	Guideline	Actionable	Venclexta (venetoclax) in combination with Cytosar-U (cytarabine) is included in guidelines for adult patients with acute myeloid leukemia harboring a FLT3 mutation (NCCN.org).	detail...
BRAF V600E	anaplastic oligodendroglioma	sensitive	Dabrafenib + Trametinib	Guideline	Actionable	Combination of Mekinist (trametinib) and Tafinlar (dabrafenib) is included in guidelines for patients with recurrent anaplastic gliomas harboring BRAF V600E, including anaplastic oligodendroglioma (NCCN.org).	detail...
NTRK1 fusion	pancreatic adenocarcinoma	sensitive	Larotrectinib	Guideline	Actionable	Vitrakvi (larotrectinib) is included in guidelines as first-line therapy for pancreatic adenocarcinoma patients harboring an NTRK fusion with locally advanced disease with good (ECOG 0-1) or intermediate (ECOG 2) performance status (PS), as first-line therapy for patients with metastatic disease with good, intermediate, or poor (ECOG 3) PS, as subsequent therapy for patients with locally advanced, metastatic, or recurrent disease with good, intermediate, or poor PS (NCCN.org).	detail...
JAK3 rearrange	childhood B-cell acute lymphoblastic leukemia	not applicable	N/A	Guideline	Prognostic	JAK3 rearrangements are associated with a poor prognosis in pediatric patients with B-cell acute lymphoblastic leukemia (NCCN.org).	detail...
RET fusion	neuroendocrine tumor	sensitive	Selpercatinib	Guideline	Actionable	Retevmo (selpercatinib) is included in guidelines for patients with unresectable or metastatic extrapulmonary poorly differentiated neuroendocrine carcinoma, large or small cell carcinoma, or mixed neuroendocrine/non-neuroendocrine neoplasms harboring RET fusions who have progressed on or following prior treatment (NCCN.org).	detail...
FGFR2 fusion	ethmoid sinus cancer	sensitive	Erdafitinib	Guideline	Actionable	Balversa (erdafitinib) is included in guidelines as subsequent-line therapy (category 2B) for patients with ethmoid sinus cancer harboring FGFR mutations or fusions and with no alternative options (NCCN.org).	detail...
FGFR2 fusion	oral cavity cancer	sensitive	Erdafitinib	Guideline	Actionable	Balversa (erdafitinib) is included in guidelines as subsequent-line therapy (category 2B) for patients with oral cavity cancer harboring FGFR mutations or fusions and with no alternative options (NCCN.org).	detail...
NTRK2 fusion	cervical cancer	sensitive	Repotrectinib	Guideline	Actionable	Augtyro (repotrectinib) is included in guidelines as second-line or subsequent therapy (category 2A) for patients with recurrent or metastatic cervical cancer harboring an NTRK fusion (NCCN.org).	detail...
DNMT3A mutant	angioimmunoblastic T-cell lymphoma	not applicable	N/A	Guideline	Diagnostic	DNMT3A mutations aid in the diagnosis of angioimmunoblastic T-cell lymphoma (NCCN.org).	detail...
MLH1 negative	esophagus adenocarcinoma	sensitive	Dostarlimab-gxly	Guideline	Actionable	Jemperli (dostarlimab-gxly) is included in guidelines as neoadjuvant, preferred first-line, second-line, or subsequent therapy for patients with unresectable locally advanced, recurrent, or metastatic esophageal adenocarcinoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
BRAF V600X	subependymal giant cell astrocytoma	sensitive	Tovorafenib	Guideline	Actionable	Ojemda (tovorafenib) is included in guidelines (category 2A) for patients with recurrent or progressive circumscribed glioma, including subependymal giant cell astrocytoma, harboring BRAF fusions, rearrangements, or BRAF V600 mutations (NCCN.org).	detail...
NTRK1 fusion	endometrial carcinoma	sensitive	Entrectinib	Guideline	Actionable	Rozlytrek (entrectinib) is included in guidelines as a second-line or subsequent-line therapy (category 2A) for patients with recurrent endometrial carcinoma harboring an NTRK fusion (NCCN.org).	detail...
NTRK1 fusion	skin melanoma	sensitive	Entrectinib	Guideline	Actionable	Rozlytrek (entrectinib) therapy is included in guidelines for patients with metastatic or unresectable cutaneous melanoma harboring an NTRK fusion (NCCN.org).	detail...
MLH1 negative	osteosarcoma	sensitive	Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab) is included in guidelines as systemic therapy for metastatic osteosarcoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
FGFR1 fusion	lung non-small cell carcinoma	sensitive	Erdafitinib	Guideline	Actionable	Balversa (erdafitinib) is included in guidelines for patients with metastatic non-small cell lung cancer harboring oncogenic or likely oncogenic FGFR alterations (NCCN.org).	detail...
MSH6 negative	bone cancer	sensitive	Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab) is included in guidelines as a systemic therapy for patients with unresectable or metastatic bone cancer with high microsatellite instability (MSI-H) or mismatch repair deficiency (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
ROS1 fusion	skin melanoma	sensitive	Crizotinib	Guideline	Actionable	Xalkori (crizotinib) is included in guidelines as second-line therapy for metastatic or unresectable cutaneous melanoma patients with ROS1 fusions (NCCN.org).	detail...
BRAF wild-type	colon cancer	predicted - sensitive	Cetuximab	Guideline	Actionable	Erbitux (cetuximab), alone and in combination with chemotherapy, is included in guidelines for patients with advanced or metastatic colon cancer that is BRAF wild-type, KRAS wild-type, and NRAS wild-type (NCCN.org).	detail...
FLT3 exon20	acute myeloid leukemia	sensitive	Gilteritinib	Guideline	Actionable	Xospata (gilteritinib) is included in guidelines for patients with relapsed or refractory acute myeloid leukemia harboring a mutation in the FLT3 tyrosine kinase domain (exons 14-23) (NCCN.org).	detail...
MSH6 negative	oropharynx cancer	sensitive	Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab) is included in guidelines as first- and subsequent-line therapy for patients with mismatch repair deficient (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) recurrent, unresectable, or metastatic oropharynx cancer (NCCN.org).	detail...
RET fusion	rectum cancer	sensitive	Selpercatinib	Guideline	Actionable	Retevmo (selpercatinib) is included in guidelines (category 2A) for patients with metastatic rectum cancer harboring RET fusion (NCCN.org).	detail...
IDH1 mutant	polycythemia vera	not applicable	N/A	Guideline	Prognostic	IDH1 mutations are associated with inferior overall survival in patients with polycythemia vera (NCCN.org).	detail...
NTRK1 fusion	appendix adenocarcinoma	sensitive	Larotrectinib	Guideline	Actionable	Vitrakvi (larotrectinib) is included in guidelines (category 2A) as second-line or subsequent therapy for patients with advanced or metastatic appendiceal adenocarcinoma harboring an NTRK fusion (NCCN.org).	detail...
IDH1 act mut	oligodendroglioma	sensitive	Vorasidenib	Guideline	Actionable	Voranigo (vorasidenib) is included in guidelines for patients with WHO grade 2 1p19q codeleted oligodendroglioma with residual/measurable disease after surgery/biopsy (category 1) or recurrent or progressive disease and WHO grade 3 1p19q codeleted oligodendroglioma with recurrent or progressive disease or as adjuvant treatment (category 2B) harboring an IDH1 activating mutation (NCCN.org).	detail...
PIK3CA mutant	Erdheim-Chester disease	sensitive	Trametinib	Guideline	Actionable	Mekinist (trametinib) is included in guidelines as first-line or subsequent-line therapy for patients with Erdheim-Chester disease harboring mutations in the MAPK pathway such as ARAF, NRAS, KRAS, MAP2K1/2, PIK3CA, or with no detectable mutations, or for whom testing is not available (NCCN.org).	detail...
TP53 loss	chronic lymphocytic leukemia/small lymphocytic lymphoma	sensitive	Acalabrutinib + Obinutuzumab	Guideline	Actionable	Calquence (acalabrutinib) combined with Gazyva (obinutuzumab) is included in guidelines as first-line therapy for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with TP53 loss (NCCN.org).	detail...
BRAF V600E	rectum cancer	resistant	Panitumumab	Guideline	Actionable	Vectibix (panitumumab), as a monotherapy, is not indicated for use in rectum cancer patients with BRAF V600E (NCCN.org).	detail...
VHL mutant	islet cell tumor	sensitive	Belzutifan	Guideline	Actionable	Welireg (belzutifan) is included in guidelines for patients with well-differentiated Grade 1/2 progressive pancreatic neuroendocrine tumors harboring germline VHL mutations (NCCN.org).	detail...
MSH6 negative	colon cancer	sensitive	Atezolizumab + Fluorouracil + Leucovorin + Oxaliplatin	Guideline	Actionable	Tecentriq (atezolizumab) in combination with Adrucil (fluorouracil), Wellcovorin (leucovorin), and Eloxatin (oxaliplatin) is included in guidelines as adjuvant therapy for patients with colon cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
FLT3 exon 14 ins	acute myeloid leukemia	sensitive	Cytarabine + Idarubicin + Midostaurin	Guideline	Actionable	Rydapt (midostaurin) in combination with Idamycin (idarubicin) and Cytosar-U (cytarabine) is included in guidelines (category 1) for patients with acute myeloid leukemia harboring a FLT3 internal tandem duplication (FLT3-ITD) mutation (NCCN.org).	detail...
NTRK1 fusion	vulva adenocarcinoma	sensitive	Entrectinib	Guideline	Actionable	Rozlytrek (entrectinib) is included in guidelines as a second-line or subsequent therapy for patients with advanced or recurrent/metastatic vulvar adenocarcinoma harboring an NTRK fusion (NCCN.org).	detail...
FGFR2 fusion	oropharynx cancer	sensitive	Erdafitinib	Guideline	Actionable	Balversa (erdafitinib) is included in guidelines as subsequent-line therapy (category 2B) for patients with oropharynx cancer harboring FGFR mutations or fusions and with no alternative options (NCCN.org).	detail...
RET Y791X	medullary thyroid carcinoma	not applicable	N/A	Guideline	Risk Factor	Germline RET Y791X mutations result in multiple endocrine neoplasia, type 2A (MEN 2A), which is associated with increased risk of developing thyroid medullary carcinoma (NCCN.org).	detail...
PTEN inact mut	colon cancer	sensitive	Aspirin	Guideline	Actionable	Aspirin is included in guidelines as adjuvant therapy (category 2A) for patients with advanced colon cancer harboring inactivating PTEN mutations, including deep deletions, and other somatic mutations affecting the PI3K pathway genes PIK3CA or PIK3R1 (NCCN.org).	detail...
FLT3 exon16	acute myeloid leukemia	sensitive	Cytarabine + Midostaurin	Guideline	Actionable	Rydapt (midostaurin) in combination with Cytosar-U (cytarabine) is included in guidelines as consolidation therapy for patients with acute myeloid leukemia harboring a mutation in the FLT3 tyrosine kinase domain (exons 14-23) (NCCN.org).	detail...
NRAS exon4	colon cancer	resistant	Cetuximab	Guideline	Actionable	Erbitux (cetuximab) is not indicated for use in colon cancer patients with NRAS exon 4 mutations (NCCN.org).	detail...
NTRK2 fusion	ampulla of Vater adenocarcinoma	sensitive	Repotrectinib	Guideline	Actionable	Augtyro (repotrectinib) is included in guidelines as first-line or subsequent therapy for patients with metastatic ampullary adenocarcinoma harboring NTRK fusions (NCCN.org).	detail...
RET fusion	gallbladder cancer	sensitive	Selpercatinib	Guideline	Actionable	Retevmo (selpercatinib) is included in guidelines as primary (category 2B) and subsequent-line therapy for patients with unresectable or metastatic biliary tract cancer harboring RET fusions, including gallbladder cancer (NCCN.org).	detail...
IDH1 mutant	myelodysplastic syndrome	sensitive	Olutasidenib	Guideline	Actionable	Rezlidhia (olutasidenib) is included in guidelines (category 2B) for patients with higher-risk myelodysplastic syndrome harboring an IDH1 mutation (NCCN.org).	detail...
MLH1 negative	colon cancer	sensitive	Tislelizumab	Guideline	Actionable	Tevimbra (tislelizumab) is included in guidelines (category 2A) for patients with advanced or metastatic colon cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
FGFR2 fusion	maxillary sinus cancer	sensitive	Erdafitinib	Guideline	Actionable	Balversa (erdafitinib) is included in guidelines as subsequent-line therapy (category 2B) for patients with maxillary sinus cancer harboring FGFR mutations or fusions and with no alternative options (NCCN.org).	detail...
NTRK2 fusion	endometrial carcinoma	sensitive	Entrectinib	Guideline	Actionable	Rozlytrek (entrectinib) is included in guidelines as a second-line or subsequent-line therapy (category 2A) for patients with recurrent endometrial carcinoma harboring an NTRK fusion (NCCN.org).	detail...
JAK2 V617F	polycythemia vera	not applicable	N/A	Guideline	Diagnostic	JAK2 V617F aids in the diagnosis of polycythemia vera (NCCN.org).	detail...
IDH1 mutant	acute myeloid leukemia	sensitive	Olutasidenib	Guideline	Actionable	Rezlidhia (olutasidenib) is included in guidelines as systemic therapy for patients with (category 2A) or without (category 2B) relapsed or refractory acute myeloid leukemia harboring an IDH1 mutation (NCCN.org).	detail...
NTRK1 fusion	oncocytic carcinoma of the thyroid	sensitive	Repotrectinib	Guideline	Actionable	Augtyro (repotrectinib) is included in guidelines for patients with RAI-refractory oncocytic thyroid carcinoma harboring an NTRK fusion with progressive or symptomatic disease (NCCN.org).	detail...
MLH1 negative	bone cancer	sensitive	Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab) is included in guidelines as a systemic therapy for patients with unresectable or metastatic bone cancer with high microsatellite instability (MSI-H) or mismatch repair deficiency (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
ROS1 rearrange	lung non-small cell carcinoma	sensitive	Crizotinib	Guideline	Actionable	Xalkori (crizotinib) is included in guidelines as first-line or subsequent therapy for patients with advanced or metastatic ROS1-rearranged non-small cell lung cancer (NCCN.org).	detail...
NTRK1 fusion	follicular thyroid carcinoma	sensitive	Entrectinib	Guideline	Actionable	Rozlytrek (entrectinib) is included in guidelines for patients with RAI-refractory oncocytic thyroid carcinoma harboring an NTRK fusion with progressive or symptomatic disease (NCCN.org).	detail...
MSH6 negative	vaginal carcinoma	sensitive	Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab) is included in guidelines as preferred second-line or subsequent therapy for patients with recurrent or metastatic vaginal squamous cell carcinoma or adenocarcinoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
MSH6 negative	small intestine adenocarcinoma	sensitive	Penpulimab-kcqx	Guideline	Actionable	Penpulimab-kcqx (AK105) is included in guidelines as systemic therapy (category 2A) for patients with advanced or metastatic small bowel adenocarcinoma with deficient mismatch repair (dMMR, often defined by the loss of MSH6, MSH2, PMS2, or MLH1 expression by IHC) (NCCN.org).	detail...
MSH6 negative	rectum cancer	sensitive	Toripalimab-tpzi	Guideline	Actionable	Loqtorz (toripalimab-tpzi) is included in guidelines (category 2A) for patients with advanced or metastatic rectal cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
MLH1 negative	small intestine adenocarcinoma	sensitive	Toripalimab-tpzi	Guideline	Actionable	Loqtorz (toripalimab-tpzi) is included in guidelines as systemic therapy (category 2A) for patients with advanced or metastatic small bowel adenocarcinoma with deficient mismatch repair (dMMR, often defined by the loss of MLH1, MSH2, MSH6, or PMS2 expression by IHC) (NCCN.org).	detail...
TP53 mutant	chronic lymphocytic leukemia/small lymphocytic lymphoma	sensitive	Acalabrutinib + Obinutuzumab	Guideline	Actionable	Calquence (acalabrutinib) combined with Gazyva (obinutuzumab) is included in guidelines as first-line therapy for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with a TP53 mutation (NCCN.org).	detail...
BRAF V600E	colon cancer	sensitive	Encorafenib + Fluorouracil + Leucovorin + Oxaliplatin + Panitumumab	Guideline	Actionable	Braftovi (encorafenib) in combination with Vectibix (panitumumab) and FOLFOX is included in guidelines as a preferred initial therapy (category 2A) for patients with advanced or metastatic colon cancer harboring BRAF V600E (NCCN.org).	detail...
BRAF L597X	melanoma	sensitive	Trametinib	Guideline	Actionable	Mekinist (trametinib) is included in guidelines as second-line therapy for metastatic or unresectable cutaneous melanoma patients with BRAF L597 mutations (NCCN.org).	detail...
MSH6 negative	pancreatic adenocarcinoma	sensitive	Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab) is included in guidelines as first-line therapy for mismatch repair-deficient (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) pancreatic adenocarcinoma patients with locally advanced disease with good (ECOG 0-1) or intermediate (ECOG 2) performance status (PS), with metastatic disease with good, intermediate, or poor (ECOG 3) PS, and as subsequent therapy for patients with locally advanced, metastatic, or recurrent disease (NCCN.org).	detail...
NRAS exon2	colon cancer	resistant	Panitumumab	Guideline	Actionable	Vectibix (panitumumab) is not indicated for use in colon cancer patients with NRAS exon 2 mutations (NCCN.org).	detail...
IDH2 wild-type	IDH-wildtype glioblastoma	not applicable	N/A	Guideline	Diagnostic	Wild-type IDH2 aids in the diagnosis of glioblastoma (NCCN.org).	detail...
JAK1 rearrange	childhood B-cell acute lymphoblastic leukemia	not applicable	N/A	Guideline	Prognostic	JAK1 rearrangements are associated with a poor prognosis in pediatric patients with B-cell acute lymphoblastic leukemia (NCCN.org).	detail...
MLH1 negative	cervical cancer	sensitive	Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab) is included in guidelines as preferred second-line or subsequent therapy for patients with cervical cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
ABL1 rearrange	myeloid neoplasm	sensitive	Imatinib	Guideline	Actionable	Gleevec (imatinib) is included in guidelines for patients with a myeloid/lymphoid neoplasm with eosinophilia harboring a ABL1 rearrangement (NCCN.org).	detail...
BRAF V600E	esophagus adenocarcinoma	sensitive	Dabrafenib + Trametinib	Guideline	Actionable	Tafinlar (dabrafenib) and Mekinist (trametinib) combination therapy is included in guidelines as second-line or subsequent therapy for patients with locally advanced, recurrent, or metastatic esophageal adenocarcinoma harboring BRAF V600E (NCCN.org).	detail...
MLH1 negative	small intestine adenocarcinoma	sensitive	Dostarlimab-gxly	Guideline	Actionable	Jemperli (dostarlimab-gxly) is included in guidelines as systemic therapy (category 2A) for patients with advanced or metastatic small bowel adenocarcinoma with deficient mismatch repair (dMMR, often defined by the loss of MLH1, MSH2, MSH6, or PMS2 expression by IHC) (NCCN.org).	detail...
BRAF V600E	rectum cancer	sensitive	Encorafenib + Panitumumab	Guideline	Actionable	Braftovi (encorafenib) in combination with Vectibix (panitumumab) is included in guidelines (category 2A) as primary or subsequent therapy for patients with rectal cancer harboring BRAF V600E (NCCN.org).	detail...
FLT3 exon21	acute myeloid leukemia	sensitive	Midostaurin	Guideline	Actionable	Rydapt (midostaurin) is included in guidelines as maintenance therapy for patients with acute myeloid leukemia harboring a mutation in the FLT3 tyrosine kinase domain (exons 14-23) (NCCN.org).	detail...
MSH6 negative	small intestine adenocarcinoma	sensitive	Dostarlimab-gxly	Guideline	Actionable	Jemperli (dostarlimab-gxly) is included in guidelines as systemic therapy (category 2A) for patients with advanced or metastatic small bowel adenocarcinoma with deficient mismatch repair (dMMR, often defined by the loss of MSH6, MSH2, PMS2, or MLH1 expression by IHC) (NCCN.org).	detail...
BRAF fusion	pilocytic astrocytoma	sensitive	Tovorafenib	Guideline	Actionable	Ojemda (tovorafenib) is included in guidelines (category 2A) for patients with recurrent or progressive circumscribed glioma, including pilocytic astrocytoma, harboring BRAF fusions, rearrangements, or BRAF V600 mutations (NCCN.org).	detail...
IDH1 mutant	acute myeloid leukemia	sensitive	Azacitidine	Guideline	Actionable	Vidaza (azacitidine) is included in guidelines for adult patients with acute myeloid leukemia harboring an IDH1 mutation (NCCN.org).	detail...
MLH1 negative	rectum cancer	sensitive	Dostarlimab-gxly	Guideline	Actionable	Jemperli (dostarlimab-gxly) is included in guidelines as subsequent therapy for patients with advanced or metastatic rectal cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
RET V804X	medullary thyroid carcinoma	not applicable	N/A	Guideline	Risk Factor	Germline RET V804X mutations result in multiple endocrine neoplasia, type 2A (MEN 2A), which is associated with increased risk of developing thyroid medullary carcinoma (NCCN.org).	detail...
ATR inact mut	prostate cancer	sensitive	Enzalutamide + Talazoparib	Guideline	Actionable	Talzenna (talazoparib) plus Xtandi (enzalutamide) is included in guidelines as systemic therapy for patients with metastatic castration-resistant prostate cancer harboring a pathogenic germline or somatic ATR mutation who have not been treated in the setting of castration-resistant prostate cancer (NCCN.org).	detail...
MLH1 negative	gallbladder cancer	sensitive	Dostarlimab-gxly	Guideline	Actionable	Jemperli (dostarlimab-gxly) is included in guidelines as subsequent therapy (category 2B) for patients with biliary tract cancer with deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC), including gallbladder cancer (NCCN.org).	detail...
TP53 loss	chronic lymphocytic leukemia/small lymphocytic lymphoma	sensitive	Idelalisib + Rituximab	Guideline	Actionable	Zydelig (idelalisib) combined with Rituxan (rituximab) is included in guidelines for patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma with TP53 loss after prior BTK inhibitor-based and BCL2 inhibitor-containing regimens (NCCN.org).	detail...
MSH6 negative	colon cancer	sensitive	Ipilimumab + Nivolumab	Guideline	Actionable	Opdivo (nivolumab), in combination with Yervoy (ipilimumab), is included in guidelines as primary or subsequent therapy for patients with advanced or metastatic colon cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
IDH2 mutant	acute myeloid leukemia	sensitive	Decitabine	Guideline	Actionable	Dacogen (decitabine) is included in guidelines for adult patients with acute myeloid leukemia harboring an IDH2 mutation (NCCN.org).	detail...
KIT exon11	gastrointestinal stromal tumor	sensitive	Imatinib	Guideline	Actionable	Gleevec (imatinib) is included in guidelines for patients with gastrointestinal stromal tumor (GIST) harboring KIT exon 11 mutations (NCCN.org).	detail...
NTRK1 fusion	papillary thyroid carcinoma	sensitive	Larotrectinib	Guideline	Actionable	Vitrakvi (larotrectinib) is included in guidelines for patients with RAI-refractory papillary thyroid carcinoma harboring an NTRK fusion with progressive or symptomatic disease (NCCN.org).	detail...
MLH1 negative	appendix adenocarcinoma	sensitive	Tislelizumab	Guideline	Actionable	Tevimbra (tislelizumab) is included in guidelines (category 2A) for patients with advanced or metastatic appendiceal adenocarcinoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
BRAF V600E	Squamous Cell Carcinoma of Unknown Primary	sensitive	Dabrafenib + Trametinib	Guideline	Actionable	The combination of Tafinlar (dabrafenib) and Mekinist (trametinib) is included in guidelines for patients with squamous cell carcinoma of unknown primary harboring BRAF V600E (NCCN.org).	detail...
BRAF V600X	skin melanoma	sensitive	Binimetinib + Encorafenib	Guideline	Actionable	Mektovi (binimetinib) and Braftovi (encorafenib) combination therapy is included in guidelines as a second-line or subsequent therapy for patients with metastatic or unresectable cutaneous melanoma harboring a BRAF V600 activating mutation (NCCN.org).	detail...
BRAF V600E	high grade glioma	sensitive	Dabrafenib + Trametinib	Guideline	Actionable	Tafinlar (dabrafenib) in combination with Mekinist (trametinib) is included in guidelines as adjuvant therapy for pediatric patients with diffuse high-grade gliomas harboring BRAF V600E, or as a preferred regimen for patients with recurrent or progressive disease (NCCN.org).	detail...
FLT3 exon16	acute myeloid leukemia	sensitive	Cytarabine + Daunorubicin + Midostaurin	Guideline	Actionable	Rydapt (midostaurin), in combination with Cerubidine (daunorubicin) and Cytosar-U (cytarabine), is included in guidelines for patients with acute myeloid leukemia harboring a mutation in the FLT3 tyrosine kinase domain (exons 14-23) (NCCN.org).	detail...
MSH6 negative	glottis cancer	sensitive	Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab) is included in guidelines as first- and subsequent-line therapy for patients with mismatch repair deficient (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) recurrent, unresectable, or metastatic glottic larynx cancer (NCCN.org).	detail...
FGFR1 act mut	oral cavity cancer	sensitive	Erdafitinib	Guideline	Actionable	Balversa (erdafitinib) is included in guidelines as subsequent-line therapy (category 2B) for patients with oral cavity cancer harboring FGFR mutations or fusions and with no alternative options (NCCN.org).	detail...
PDGFRB rearrange	childhood B-cell acute lymphoblastic leukemia	not applicable	N/A	Guideline	Prognostic	PDGFRB rearrangements are associated with a poor prognosis in pediatric patients with B-cell acute lymphoblastic leukemia (NCCN.org).	detail...
NTRK2 fusion	stomach cancer	sensitive	Larotrectinib	Guideline	Actionable	Vitrakvi (larotrectinib) is included in guidelines as second-line or subsequent therapy for patients with unresectable locally advanced, recurrent, or metastatic gastric cancer harboring an NTRK2 fusion (NCCN.org).	detail...
FLT3 exon 14 ins	acute myeloid leukemia	sensitive	Gilteritinib	Guideline	Actionable	Xospata (gilteritinib) is included in the guidelines for patients with relapsed or refractory acute myeloid leukemia harboring a FLT3 internal tandem duplication (FLT3-ITD) mutation (NCCN.org).	detail...
MLH1 mutant	ovarian cancer	not applicable	N/A	Guideline	Risk Factor	Germline mutations in MLH1 result in Lynch syndrome, which is associated with increased risk of ovarian cancer (NCCN.org).	detail...
MLH1 negative	appendix adenocarcinoma	sensitive	Toripalimab-tpzi	Guideline	Actionable	Loqtorz (toripalimab-tpzi) is included in guidelines (category 2A) for patients with advanced or metastatic appendiceal adenocarcinoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
FGFR3 fusion	salivary gland cancer	sensitive	Erdafitinib	Guideline	Actionable	Balversa (erdafitinib) is included in guidelines for patients with unresectable locally advanced, recurrent, or metastatic salivary gland tumors harboring FGFR mutations or fusions (category 2B) who received prior systemic therapy and have no alternative systemic therapy available (NCCN.org).	detail...
MSH6 negative	oral cavity cancer	sensitive	Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab) is included in guidelines as first- and subsequent-line therapy for patients with mismatch repair deficient (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) recurrent, unresectable, or metastatic oral cavity cancer (NCCN.org).	detail...
FLT3 exon21	acute myeloid leukemia	sensitive	Cytarabine + Midostaurin	Guideline	Actionable	Rydapt (midostaurin) in combination with Cytosar-U (cytarabine) is included in guidelines as consolidation therapy for patients with acute myeloid leukemia harboring a mutation in the FLT3 tyrosine kinase domain (exons 14-23) (NCCN.org).	detail...
NTRK2 fusion	soft tissue sarcoma	sensitive	Entrectinib	Guideline	Actionable	Rozlytrek (entrectinib) is in guidelines for patients with soft tissue sarcoma harboring an NTRK fusion (NCCN.org).	detail...
BRAF V600E	ganglioglioma	sensitive	Cobimetinib + Vemurafenib	Guideline	Actionable	Zelboraf (vemurafenib) and Cotellic (cobimetinib) combination therapy is included in guidelines as an adjuvant treatment for patients with ganglioglioma harboring BRAF V600E (NCCN.org).	detail...
NTRK1 fusion	pancreatic adenocarcinoma	sensitive	Entrectinib	Guideline	Actionable	Rozlytrek (entrectinib) is included in guidelines as first-line therapy for pancreatic adenocarcinoma patients harboring an NTRK fusion with locally advanced disease with good (ECOG 0-1) or intermediate (ECOG 2) performance status (PS), as first-line therapy for patients with metastatic disease with good, intermediate (category 2A), or poor (ECOG 3) (category 2B) PS, as subsequent therapy for patients with locally advanced, metastatic, or recurrent disease (NCCN.org).	detail...
MLH1 negative	esophagus squamous cell carcinoma	sensitive	Capecitabine + Nivolumab + Oxaliplatin	Guideline	Actionable	Opdivo (nivolumab), in combination with Xeloda (capecitabine) and Eloxatin (oxaliplatin) is included in guidelines as first-line therapy for patients with unresectable locally advanced, recurrent, or metastatic esophagus squamous cell carcinoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
RET fusion	ovary epithelial cancer	sensitive	Selpercatinib	Guideline	Actionable	Retevmo (selpercatinib) is included in guidelines as systemic therapy for patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer harboring a RET fusion (NCCN.org).	detail...
NTRK2 fusion	ovary epithelial cancer	sensitive	Larotrectinib	Guideline	Actionable	Vitrakvi (larotrectinib) is included in guidelines as systemic therapy for patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer harboring an NTRK fusion (NCCN.org).	detail...
KMT2A rearrange	childhood T-cell acute lymphoblastic leukemia	sensitive	Revumenib	Guideline	Actionable	Revuforj (revumenib) is included in guidelines for pediatric patients with relapsed or refractory T-cell acute lymphoblastic leukemia harboring a KMT2A rearrangement (NCCN.org).	detail...
BRAF V600E	salivary gland cancer	sensitive	Dabrafenib + Trametinib	Guideline	Actionable	Tafinlar (dabrafenib) and Mekinist (trametinib) combination therapy is included in guidelines (category 2A) for patients with recurrent, unresectable, or metastatic salivary gland tumors harboring BRAF V600E (NCCN.org).	detail...
MLH1 negative	appendix adenocarcinoma	sensitive	Dostarlimab-gxly	Guideline	Actionable	Jemperli (dostarlimab-gxly) is included in guidelines (category 2A) for patients with advanced or metastatic appendiceal adenocarcinoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
BRAF V600X	skin melanoma	sensitive	Dabrafenib	Guideline	Actionable	Tafinlar (dabrafenib) therapy is included in guidelines for patients with unresectable or metastatic cutaneous melanoma harboring BRAF V600 activating mutations, in cases where BRAF/MEK inhibitor combination therapy is contraindicated (NCCN.org).	detail...
NTRK2 fusion	Squamous Cell Carcinoma of Unknown Primary	sensitive	Entrectinib	Guideline	Actionable	Rozlytrek (entrectinib) is included in guidelines for patients with squamous cell carcinoma of unknown primary harboring NTRK2 fusions (NCCN.org).	detail...
MLH1 negative	ampulla of Vater adenocarcinoma	sensitive	Ipilimumab + Nivolumab	Guideline	Actionable	Opdivo (nivolumab) and Yervoy (ipilimumab) combination therapy is included in guidelines as first-line or subsequent therapy for metastatic ampullary adenocarcinoma patients with deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
MSH6 negative	papillary thyroid carcinoma	sensitive	Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab) is included in guidelines for patients with papillary thyroid carcinoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) after progression on prior treatment (NCCN.org).	detail...
RET S891X	medullary thyroid carcinoma	not applicable	N/A	Guideline	Risk Factor	Germline RET S891X mutations result in multiple endocrine neoplasia, type 2A (MEN 2A), which is associated with increased risk of developing thyroid medullary carcinoma (NCCN.org).	detail...
MAP2K1 mutant	Erdheim-Chester disease	sensitive	Cobimetinib	Guideline	Actionable	Cotellic (cobimetinib) is included in guidelines as preferred first-line or subsequent-line therapy for patients with Erdheim-Chester disease harboring mutations in the MAPK pathway such as ARAF, NRAS, KRAS, MAP2K1/2, PIK3CA, or with no detectable mutations, or for whom testing is not available (NCCN.org).	detail...
MLH1 negative	small intestine adenocarcinoma	sensitive	Retifanlimab	Guideline	Actionable	Zynyz (retifanlimab) is included in guidelines as systemic therapy (category 2A) for patients with advanced or metastatic small bowel adenocarcinoma with deficient mismatch repair (dMMR, often defined by the loss of MLH1, MSH2, MSH6, or PMS2 expression by IHC) (NCCN.org).	detail...
MSH6 negative	colon cancer	sensitive	Cosibelimab	Guideline	Actionable	Unloxcyt (cosibelimab) is included in guidelines (category 2A) for patients with advanced or metastatic colon cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MSH6, MSH2, MLH1, or PMS2 expression by IHC) (NCCN.org).	detail...
MSH6 negative	rectum cancer	sensitive	Atezolizumab	Guideline	Actionable	Tecentriq (atezolizumab) is included in guidelines (category 2A) for patients with advanced or metastatic rectal cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MSH6, MSH2, MLH1, or PMS2 expression by IHC) (NCCN.org).	detail...
MSH6 negative	Ewing sarcoma	sensitive	Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab) is included in guidelines as systemic therapy for metastatic Ewing sarcoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
NTRK1 fusion	glioblastoma	sensitive	Entrectinib	Guideline	Actionable	Rozlytrek (entrectinib) is included in guidelines for patients with recurrent glioblastoma harboring an NTRK fusion (NCCN.org).	detail...
NTRK1 fusion	high grade glioma	sensitive	Repotrectinib	Guideline	Actionable	Augtyro (repotrectinib) is included in guidelines as adjuvant therapy for pediatric patients with diffuse high-grade gliomas harboring NTRK fusions, or as a preferred regimen for patients with recurrent or progressive disease (NCCN.org).	detail...
FGFR1 fusion	ethmoid sinus cancer	sensitive	Erdafitinib	Guideline	Actionable	Balversa (erdafitinib) is included in guidelines as subsequent-line therapy (category 2B) for patients with ethmoid sinus cancer harboring FGFR mutations or fusions and with no alternative options (NCCN.org).	detail...
MSH6 negative	stomach cancer	sensitive	Dostarlimab-gxly	Guideline	Actionable	Jemperli (dostarlimab-gxly) is included in guidelines as first-line, second-line, or subsequent therapy for patients with unresectable locally advanced or metastatic gastric cancer with deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
FGFR3 act mut	hypopharynx cancer	sensitive	Erdafitinib	Guideline	Actionable	Balversa (erdafitinib) is included in guidelines as subsequent-line therapy (category 2B) for patients with hypopharynx cancer harboring FGFR mutations or fusions and with no alternative options (NCCN.org).	detail...
BRAF V600E	appendix adenocarcinoma	sensitive	Encorafenib + Panitumumab	Guideline	Actionable	Braftovi (encorafenib) in combination with Vectibix (panitumumab) is included in guidelines (category 2A) for patients with advanced or metastatic appendiceal adenocarcinoma harboring BRAF V600E (NCCN.org).	detail...
MSH6 negative	small intestine adenocarcinoma	sensitive	Tislelizumab	Guideline	Actionable	Tevimbra (tislelizumab) is included in guidelines as systemic therapy (category 2A) for patients with advanced or metastatic small bowel adenocarcinoma with deficient mismatch repair (dMMR, often defined by the loss of MSH6, MSH2, PMS2, or MLH1 expression by IHC) (NCCN.org).	detail...
KIT D816X	systemic mastocytosis	not applicable	N/A	Guideline	Diagnostic	Activating mutations at codon 816 of KIT aid in the diagnosis of systemic mastocytosis (NCCN.org).	detail...
NTRK1 fusion	small intestine adenocarcinoma	sensitive	Repotrectinib	Guideline	Actionable	Augtyro (repotrectinib) is included in guidelines as second-line or subsequent therapy (category 2A) for patients with advanced or metastatic small bowel adenocarcinoma harboring an NTRK fusion (NCCN.org).	detail...
RET fusion	gallbladder cancer	sensitive	Pralsetinib	Guideline	Actionable	Gavreto (pralsetinib) is included in guidelines as primary (category 2B) and subsequent-line therapy (category 2B) for patients with unresectable or metastatic biliary tract cancer harboring RET fusions, including gallbladder cancer (NCCN.org).	detail...
VHL inact mut	paraganglioma	not applicable	N/A	Guideline	Risk Factor	Germline inactivating mutations in VHL result in von Hippel-Lindau (VHL) syndrome, which is associated with increased risk of developing paraganglioma (NCCN.org).	detail...
NTRK2 fusion	gastrointestinal stromal tumor	sensitive	Entrectinib	Guideline	Actionable	Rozlytrek (entrectinib) is included in guidelines as neoadjuvant therapy for patients with resectable disease and as first-line systemic therapy for patients with unresectable or metastatic gastrointestinal stromal tumor (GIST) harboring NTRK fusions (NCCN.org).	detail...
MSH6 negative	oncocytic carcinoma of the thyroid	sensitive	Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab) is included in guidelines for patients with Hurthle cell thyroid carcinoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) after progression on prior treatment (NCCN.org).	detail...
JAK2 rearrange	myeloid neoplasm	sensitive	Momelotinib	Guideline	Actionable	Momelotinib (CYT387) is included in guidelines for patients with a myeloid/lymphoid neoplasm with eosinophilia harboring a JAK2 rearrangement (NCCN.org).	detail...
IDH2 R172X	myelodysplastic syndrome	not applicable	N/A	Guideline	Prognostic	IDH2 R172X is associated with a poor prognosis in patients with myelodysplastic syndrome (NCCN.org).	detail...
NTRK1 fusion	gastrointestinal stromal tumor	sensitive	Entrectinib	Guideline	Actionable	Rozlytrek (entrectinib) is included in guidelines as neoadjuvant therapy for patients with resectable disease and as first-line systemic therapy for patients with unresectable or metastatic gastrointestinal stromal tumor (GIST) harboring NTRK fusions (NCCN.org).	detail...
NTRK2 fusion	glioblastoma	sensitive	Entrectinib	Guideline	Actionable	Rozlytrek (entrectinib) is included in guidelines for patients with recurrent glioblastoma harboring an NTRK fusion (NCCN.org).	detail...
RET fusion	paraganglioma	sensitive	Selpercatinib	Guideline	Actionable	Retevmo (selpercatinib) is included in guidelines for patients with RET fusion-positive, locally unresectable or metastatic paraganglioma (NCCN.org).	detail...
MSH6 negative	intrahepatic cholangiocarcinoma	sensitive	Dostarlimab-gxly	Guideline	Actionable	Jemperli (dostarlimab-gxly) is included in guidelines as subsequent therapy (category 2B) for patients with biliary tract cancer with deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC), including intrahepatic cholangiocarcinoma (NCCN.org).	detail...
MLH1 negative	rectum cancer	sensitive	Cosibelimab	Guideline	Actionable	Unloxcyt (cosibelimab) is included in guidelines (category 2A) for patients with advanced or metastatic rectal cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, MSH2, MSH6, or PMS2 expression by IHC) (NCCN.org).	detail...
NTRK1 fusion	glioblastoma	sensitive	Larotrectinib	Guideline	Actionable	Vitrakvi (larotrectinib) is included in guidelines for patients with recurrent glioblastoma harboring an NTRK fusion (NCCN.org).	detail...
FGFR2 act mut	hypopharynx cancer	sensitive	Erdafitinib	Guideline	Actionable	Balversa (erdafitinib) is included in guidelines as subsequent-line therapy (category 2B) for patients with hypopharynx cancer harboring FGFR mutations or fusions and with no alternative options (NCCN.org).	detail...
TP53 mutant	myelodysplastic syndrome	not applicable	N/A	Guideline	Prognostic	TP53 mutations except P47S and P72R are associated with a poor prognosis in patients with myelodysplastic syndrome (NCCN.org).	detail...
MSH6 negative	colon cancer	sensitive	Atezolizumab	Guideline	Actionable	Tecentriq (atezolizumab) is included in guidelines (category 2A) for patients with advanced or metastatic colon cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MSH6, MSH2, MLH1, or PMS2 expression by IHC) (NCCN.org).	detail...
MSH6 negative	colon cancer	sensitive	Durvalumab	Guideline	Actionable	Imfinzi (durvalumab) is included in guidelines (category 2A) for patients with advanced or metastatic colon cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MSH6, MSH2, MLH1, or PMS2 expression by IHC) (NCCN.org).	detail...
MLH1 negative	Adenocarcinoma of Unknown Primary	sensitive	Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab) is included in guidelines for patients with adenocarcinoma of unknown primary with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
MSH6 negative	neuroendocrine tumor	sensitive	Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab) is included in guidelines for patients with mismatch repair deficient (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) locally advanced or metastatic well-differentiated, Grade 3 neuroendocrine tumors or unresectable or metastatic extrapulmonary poorly differentiated neuroendocrine carcinoma, large or small cell carcinoma, or mixed neuroendocrine/non-neuroendocrine neoplasms who have progressed on or following prior treatment (NCCN.org).	detail...
NTRK1 fusion	Squamous Cell Carcinoma of Unknown Primary	sensitive	Entrectinib	Guideline	Actionable	Rozlytrek (entrectinib) is included in guidelines for patients with squamous cell carcinoma of unknown primary harboring NTRK1 fusions (NCCN.org).	detail...
NTRK2 fusion	intrahepatic cholangiocarcinoma	sensitive	Entrectinib	Guideline	Actionable	Rozlytrek (entrectinib) is included in guidelines as primary and subsequent-line therapy for patients with unresectable or metastatic biliary tract cancer harboring an NTRK fusion, including intrahepatic cholangiocarcinoma (NCCN.org).	detail...
FGFR1 fusion	breast cancer	sensitive	Erdafitinib	Guideline	Actionable	Balversa (erdafitinib) is included in guidelines for patients with stage IV (M1) breast cancer harboring FGFR fusion or mutations (category 2B) (NCCN.org).	detail...
FLT3 exon 15 ins	acute myeloid leukemia	sensitive	Decitabine + Sorafenib	Guideline	Actionable	Nexavar (sorafenib) in combination with Dacogen (decitabine) is included in guidelines for patients with relapsed or refractory acute myeloid leukemia harboring a FLT3 internal tandem duplication (FLT3-ITD) mutation (NCCN.org).	detail...
FGFR1 act mut	supraglottis cancer	sensitive	Erdafitinib	Guideline	Actionable	Balversa (erdafitinib) is included in guidelines as subsequent-line therapy (category 2B) for patients with supraglottic larynx cancer harboring FGFR mutations or fusions and with no alternative options (NCCN.org).	detail...
ALK rearrange	inflammatory myofibroblastic tumor	sensitive	Ceritinib	Guideline	Actionable	Zykadia (ceritinib) is included in guidelines as first-line therapy for patients with advanced, recurrent, metastatic, or inoperable inflammatory myofibroblastic tumor harboring ALK translocations (NCCN.org).	detail...
NTRK2 fusion	rectum cancer	sensitive	Entrectinib	Guideline	Actionable	Rozlytrek (entrectinib) is included in guidelines for advanced or metastatic rectal cancer patients with an NTRK fusion (NCCN.org).	detail...
NTRK2 fusion	lung non-small cell carcinoma	sensitive	Larotrectinib	Guideline	Actionable	Vitrakvi (larotrectinib) is included in guidelines as first-line or subsequent therapy for patients with advanced or metastatic non-small cell lung cancer harboring an NTRK2 fusion (NCCN.org).	detail...
BTK C481S	chronic lymphocytic leukemia/small lymphocytic lymphoma	resistant	Zanubrutinib	Guideline	Actionable	Brukinsa (zanubrutinib) is not indicated for use in patients with Imbruvica (ibrutinib)-refractory chronic lymphocytic leukemia/small lymphocytic lymphoma harboring BTK C481S (NCCN.org).	detail...
IDH2 mutant	anaplastic astrocytoma	not applicable	N/A	Guideline	Diagnostic	IDH2 mutations aid in the diagnosis of grade III astrocytomas (NCCN.org).	detail...
JAK3 mutant	B-cell acute lymphoblastic leukemia	not applicable	N/A	Guideline	Prognostic	JAK3 mutations are associated with a poor prognosis in patients with B-cell acute lymphoblastic leukemia (NCCN.org).	detail...
JAK2 mutant	essential thrombocythemia	not applicable	N/A	Guideline	Diagnostic	JAK2 mutations aid in the diagnosis of essential thrombocythemia (NCCN.org).	detail...
TP53 mutant	B-cell acute lymphoblastic leukemia	not applicable	N/A	Guideline	Prognostic	TP53 mutations are associated with poor prognosis in patients with B-cell acute lymphoblastic leukemia (NCCN.org).	detail...
TP53 loss	chronic lymphocytic leukemia/small lymphocytic lymphoma	sensitive	Lisocabtagene maraleucel	Guideline	Actionable	Breyanzi (lisocabtagene maraleucel) is included in guidelines for patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma with TP53 loss after prior BTK inhibitor-based and BCL2 inhibitor-containing regimens (NCCN.org).	detail...
FGFR2 fusion	glottis cancer	sensitive	Erdafitinib	Guideline	Actionable	Balversa (erdafitinib) is included in guidelines as subsequent-line therapy (category 2B) for patients with glottic larynx cancer harboring FGFR mutations or fusions and with no alternative options (NCCN.org).	detail...
MLH1 negative	esophagus adenocarcinoma	sensitive	Fluorouracil + Oxaliplatin + Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab), in combination with Adrucil (fluorouracil) and Eloxatin (oxaliplatin) is included in guidelines as first-line therapy for patients with unresectable locally advanced, recurrent, or metastatic esophageal adenocarcinoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
MLH1 negative	pancreatic adenocarcinoma	sensitive	Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab) is included in guidelines as first-line therapy for mismatch repair-deficient (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) pancreatic adenocarcinoma patients with locally advanced disease with good (ECOG 0-1) or intermediate (ECOG 2) performance status (PS), with metastatic disease with good, intermediate, or poor (ECOG 3) PS, and as subsequent therapy for patients with locally advanced, metastatic, or recurrent disease (NCCN.org).	detail...
FLT3 exon18	acute myeloid leukemia	sensitive	Gilteritinib	Guideline	Actionable	Xospata (gilteritinib) is included in guidelines for patients with relapsed or refractory acute myeloid leukemia harboring a mutation in the FLT3 tyrosine kinase domain (exons 14-23) (NCCN.org).	detail...
NTRK2 fusion	ovary epithelial cancer	sensitive	Entrectinib	Guideline	Actionable	Rozlytrek (entrectinib) is included in guidelines as systemic therapy for patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer harboring an NTRK fusion (NCCN.org).	detail...
MLH1 mutant	endometrial carcinoma	not applicable	N/A	Guideline	Risk Factor	Germline mutations in MLH1 result in Lynch syndrome, which is associated with increased risk of developing endometrial carcinoma (NCCN.org).	detail...
IDH1 mutant	myelofibrosis	not applicable	N/A	Guideline	Diagnostic	IDH1 mutations aid in the diagnosis of primary myelofibrosis in the absence of JAK2, CALR, or MPL mutations (NCCN.org).	detail...
TP53 mutant	chronic lymphocytic leukemia/small lymphocytic lymphoma	sensitive	Methylprednisolone + Rituximab	Guideline	Actionable	Artisone-Wyeth (methylprednisolone) combined with Rituxan (rituximab) is included in guidelines as first-line therapy for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with a TP53 mutation and for patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma with a TP53 mutation after prior BTK inhibitor-based and BCL2 inhibitor-containing regimens (NCCN.org).	detail...
NTRK1 fusion	esophagus squamous cell carcinoma	sensitive	Entrectinib	Guideline	Actionable	Rozlytrek (entrectinib) is included in guidelines as second-line or subsequent therapy for patients with unresectable locally advanced, recurrent, or metastatic esophageal squamous cell carcinoma with an NTRK fusion (NCCN.org).	detail...
MSH6 negative	small intestine adenocarcinoma	sensitive	Toripalimab-tpzi	Guideline	Actionable	Loqtorz (toripalimab-tpzi) is included in guidelines as systemic therapy (category 2A) for patients with advanced or metastatic small bowel adenocarcinoma with deficient mismatch repair (dMMR, often defined by the loss of MSH6, MSH2, PMS2, or MLH1 expression by IHC) (NCCN.org).	detail...
MLH1 negative	Squamous Cell Carcinoma of Unknown Primary	sensitive	Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab) is included in guidelines for patients with squamous cell carcinoma of unknown primary with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
MLH1 negative	colon cancer	sensitive	Nivolumab	Guideline	Actionable	Opdivo (nivolumab) is included in guidelines as primary or subsequent therapy for patients with advanced or metastatic colon cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
MSH6 negative	colon cancer	sensitive	Retifanlimab	Guideline	Actionable	Zynyz (retifanlimab) is included in guidelines (category 2A) for patients with advanced or metastatic colon cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
MSH6 negative	rectum cancer	sensitive	Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab) is included in guidelines as a preferred primary therapy for advanced or metastatic rectum cancer patients with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
RET C611X	medullary thyroid carcinoma	not applicable	N/A	Guideline	Risk Factor	Germline RET C611X mutations result in multiple endocrine neoplasia, type 2A (MEN 2A), which is associated with high risk of developing thyroid medullary carcinoma (NCCN.org).	detail...
RET V804M RET S904C	medullary thyroid carcinoma	not applicable	N/A	Guideline	Risk Factor	Compound germline RET V804M and S904C mutations result in multiple endocrine neoplasia, type 2B (MEN 2B), which is associated with high risk of developing thyroid medullary carcinoma (NCCN.org).	detail...
TP53 loss	chronic lymphocytic leukemia/small lymphocytic lymphoma	sensitive	Ibrutinib + Venetoclax	Guideline	Actionable	Venclexta (venetoclax) combined with Imbruvica (ibrutinib) is included in guidelines as first-line (category 2A), second-line, or third-line therapy (category 2B) for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with TP53 loss (NCCN.org).	detail...
MSH6 negative	osteosarcoma	sensitive	Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab) is included in guidelines as systemic therapy for metastatic osteosarcoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
MLH1 negative	esophagus squamous cell carcinoma	sensitive	Capecitabine + Oxaliplatin + Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab), in combination with Xeloda (capecitabine) and Eloxatin (oxaliplatin) is included in guidelines as first-line therapy for patients with unresectable locally advanced, recurrent, or metastatic esophagus squamous cell carcinoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
BRAF V600E	colon cancer	sensitive	Cetuximab + Encorafenib + Fluorouracil + Leucovorin + Oxaliplatin	Guideline	Actionable	Braftovi (encorafenib) in combination with Erbitux (cetuximab) and FOLFOX is included in guidelines as a preferred initial therapy (category 2A) for patients with advanced or metastatic colon cancer harboring BRAF V600E (NCCN.org).	detail...
MSH6 negative	follicular thyroid carcinoma	sensitive	Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab) is included in guidelines for patients with follicular thyroid carcinoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) after progression on prior treatment (NCCN.org).	detail...
MLH1 negative	extrahepatic bile duct carcinoma	sensitive	Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab) is included in guidelines as primary therapy and subsequent-line therapy for patients with unresectable or metastatic biliary tract cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC), including extrahepatic cholangiocarcinoma (NCCN.org).	detail...
MLH1 negative	colon cancer	sensitive	Toripalimab-tpzi	Guideline	Actionable	Loqtorz (toripalimab-tpzi) is included in guidelines (category 2A) for patients with advanced or metastatic colon cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
IDH1 mutant	high grade glioma	not applicable	N/A	Guideline	Prognostic	IDH1 mutations are associated with a favorable prognosis in patients with glioma, and are associated with a survival benefit for patients treated with radiation or alkylator therapy (NCCN.org).	detail...
FGFR3 act mut	lung non-small cell carcinoma	sensitive	Erdafitinib	Guideline	Actionable	Balversa (erdafitinib) is included in guidelines for patients with metastatic non-small cell lung cancer harboring oncogenic or likely oncogenic FGFR alterations (NCCN.org).	detail...
PIK3CA inact mut	rectum cancer	sensitive	Aspirin	Guideline	Actionable	Aspirin is included in guidelines as adjuvant therapy (category 2A) for patients with advanced rectal cancer harboring PIK3CA mutations, including hotspot mutations in exon 10 (reported as exon 9) and exon 21 (reported as exon 20), and other somatic mutations affecting the PI3K pathway genes PIK3R1 or PTEN (NCCN.org).	detail...
FGFR1 rearrange	B-cell acute lymphoblastic leukemia	not applicable	N/A	Guideline	Prognostic	FGFR1 rearrangements are associated with a poor prognosis in patients with B-cell acute lymphoblastic leukemia (NCCN.org).	detail...
MLH1 negative	salivary gland cancer	sensitive	Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab) is included in guidelines for patients with recurrent, unresectable, or metastatic salivary gland tumors with deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
FLT3 exon 15 ins	acute myeloid leukemia	sensitive	Quizartinib	Guideline	Actionable	Vanflyta (quizartinib) is included in guidelines as maintenance therapy for patients with acute myeloid leukemia harboring a FLT3 internal tandem duplication (FLT3-ITD) mutation (NCCN.org).	detail...
TP53 mutant	breast cancer	not applicable	N/A	Guideline	Risk Factor	Germline TP53 mutations result in Li-Fraumeni syndrome, which is associated with increased risk of developing breast cancer (NCCN.org).	detail...
NTRK1 fusion	glioblastoma	sensitive	Repotrectinib	Guideline	Actionable	Augtyro (repotrectinib) is included in guidelines (category 2B) for patients with recurrent glioblastoma harboring an NTRK fusion (NCCN.org).	detail...
FLT3 exon 15 ins	myelodysplastic syndrome	not applicable	N/A	Guideline	Prognostic	FLT3 internal tandem duplication (FLT3-ITD) mutations are associated with poor prognosis in patients with myelodysplastic syndrome (NCCN.org).	detail...
ABL1 rearrange	myeloid neoplasm	sensitive	Dasatinib	Guideline	Actionable	Sprycel (dasatinib) is included in guidelines as a preferred regimen for patients with a myeloid/lymphoid neoplasm with eosinophilia harboring a ABL1 rearrangement (NCCN.org).	detail...
MSH6 negative	esophagus adenocarcinoma	sensitive	Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab) is included in guidelines as first-line, second-line, or subsequent therapy for patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) esophageal adenocarcinoma that are unresectable, locally advanced, recurrent, or metastatic (NCCN.org).	detail...
NTRK1 fusion	soft tissue sarcoma	sensitive	Larotrectinib	Guideline	Actionable	Vitrakvi (larotrectinib) is in guidelines for patients with soft tissue sarcoma harboring an NTRK fusion (NCCN.org).	detail...
MLH1 negative	colon cancer	sensitive	Durvalumab	Guideline	Actionable	Imfinzi (durvalumab) is included in guidelines (category 2A) for patients with advanced or metastatic colon cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, MSH2, MSH6, or PMS2 expression by IHC) (NCCN.org).	detail...
NTRK2 fusion	breast cancer	sensitive	Entrectinib	Guideline	Actionable	Rozlytrek (entrectinib) therapy is included in guidelines for patients with recurrent unresectable or stage IV (M1) breast cancer harboring an NTRK fusion (NCCN.org).	detail...
FLT3 exon 14 ins	acute myeloid leukemia	sensitive	Quizartinib	Guideline	Actionable	Vanflyta (quizartinib) is included in guidelines as maintenance therapy for patients with acute myeloid leukemia harboring a FLT3 internal tandem duplication (FLT3-ITD) mutation (NCCN.org).	detail...
MSH6 negative	endometrial carcinoma	sensitive	Retifanlimab	Guideline	Actionable	Zynyz (retifanlimab) is included in guidelines as a second-line or subsequent-line therapy (category 2B) for patients with high microsatellite instability (MSI-H) or mismatch repair-deficient (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) recurrent endometrial carcinoma (NCCN.org).	detail...
NTRK1 fusion	uterine corpus sarcoma	sensitive	Larotrectinib	Guideline	Actionable	Vitrakvi (larotrectinib) is included in guidelines as first-line therapy for patients with advanced, recurrent, metastatic, or inoperable uterine sarcoma harboring an NTRK fusion (NCCN.org).	detail...
MLH1 negative	vulva adenocarcinoma	sensitive	Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab) is included in guidelines as a second-line or subsequent therapy for patients with advanced or recurrent/metastatic MSI high or dMMR (often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) vulva adenocarcinoma (NCCN.org).	detail...
MLH1 mutant	rectum cancer	not applicable	N/A	Guideline	Risk Factor	Lynch syndrome results from germline mutations in DNA mismatch repair genes including MLH1, MSH2, MSH6, and PMS2, and is associated with increased risk of developing colorectal cancer (NCCN.org).	detail...
FLT3 mutant	acute myeloid leukemia	sensitive	Decitabine + Venetoclax	Guideline	Actionable	Venclexta (venetoclax) in combination with Dacogen (decitabine) is included in guidelines for adult patients with acute myeloid leukemia harboring a FLT3 mutation (NCCN.org).	detail...
MSH6 negative	esophagus adenocarcinoma	sensitive	Ipilimumab + Nivolumab	Guideline	Actionable	Opdivo (nivolumab), in combination with Yervoy (ipilimumab), is included in guidelines as first-line, second-line, or subsequent therapy for patients with unresectable locally advanced, recurrent, or metastatic esophageal adenocarcinoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
FLT3 exon 15 ins	acute myeloid leukemia	not applicable	N/A	Guideline	Prognostic	FLT3 internal tandem duplication (FLT3-ITD) mutations are associated with inferior prognosis in acute myeloid leukemia patients with normal karyotype (NCCN.org).	detail...
NTRK2 fusion	vaginal carcinoma	sensitive	Larotrectinib	Guideline	Actionable	Vitrakvi (larotrectinib) is included in guidelines as second-line or subsequent therapy for patients with recurrent or metastatic vaginal squamous cell carcinoma or adenocarcinoma harboring an NTRK fusion (NCCN.org).	detail...
MSH6 negative	gallbladder cancer	sensitive	Dostarlimab-gxly	Guideline	Actionable	Jemperli (dostarlimab-gxly) is included in guidelines as subsequent therapy (category 2B) for patients with biliary tract cancer with deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC), including gallbladder cancer (NCCN.org).	detail...
MSH6 negative	gastroesophageal junction adenocarcinoma	sensitive	Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab) is included in guidelines as first-line, second-line, or subsequent therapy for patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) gastroesophageal junction cancer that are unresectable, locally advanced, recurrent, or metastatic (NCCN.org).	detail...
FLT3 exon15	acute myeloid leukemia	sensitive	Gilteritinib	Guideline	Actionable	Xospata (gilteritinib) is included in guidelines for patients with relapsed or refractory acute myeloid leukemia harboring a mutation in the FLT3 tyrosine kinase domain (exons 14-23) (NCCN.org).	detail...
RET C609X	medullary thyroid carcinoma	not applicable	N/A	Guideline	Risk Factor	Germline RET C609X mutations result in multiple endocrine neoplasia, type 2A (MEN 2A), which is associated with increased risk of developing thyroid medullary carcinoma (NCCN.org).	detail...
MSH6 negative	vulva squamous cell carcinoma	sensitive	Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab) is included in guidelines as a second-line or subsequent therapy for patients with advanced or recurrent/metastatic MSI high or dMMR (often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) vulva squamous cell carcinoma (NCCN.org).	detail...
ALK fusion	Erdheim-Chester disease	sensitive	Ceritinib	Guideline	Actionable	Zykadia (ceritinib) is included in guidelines as first-line or subsequent-line therapy for patients with Erdheim-Chester disease harboring ALK fusions (NCCN.org).	detail...
MLH1 negative	papillary thyroid carcinoma	sensitive	Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab) is included in guidelines for patients with papillary thyroid carcinoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) after progression on prior treatment (NCCN.org).	detail...
NTRK1 fusion	anaplastic thyroid carcinoma	sensitive	Repotrectinib	Guideline	Actionable	Augtyro (repotrectinib) is included in guidelines as neoadjuvant treatment for anaplastic thyroid carcinoma patients harboring NTRK fusions with stage IVa or IVb borderline resectable disease, and as a preferred systemic therapy for those with metastatic disease (NCCN.org).	detail...
MSH6 negative	rectum cancer	sensitive	Nivolumab	Guideline	Actionable	Opdivo (nivolumab) is included in guidelines as a primary therapy for advanced or metastatic rectum cancer patients with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
BRAF V600E	oncocytic carcinoma of the thyroid	sensitive	Dabrafenib + Trametinib	Guideline	Actionable	The combination of Tafinlar (dabrafenib) and Mekinist (trametinib) is included in guidelines for patients with RAI-refractory oncocytic thyroid carcinoma harboring BRAF V600E who have progressed on therapy and have no further treatment options (NCCN.org).	detail...
MLH1 negative	colon cancer	sensitive	Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab) is included in guidelines as preferred primary or subsequent therapy for patients with advanced or metastatic colon cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
FGFR2 fusion	lung non-small cell carcinoma	sensitive	Erdafitinib	Guideline	Actionable	Balversa (erdafitinib) is included in guidelines for patients with metastatic non-small cell lung cancer harboring oncogenic or likely oncogenic FGFR alterations (NCCN.org).	detail...
MSH6 negative	Adenocarcinoma of Unknown Primary	sensitive	Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab) is included in guidelines for patients with adenocarcinoma of unknown primary with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
IDH1 mutant	myelodysplastic syndrome	sensitive	Azacitidine + Olutasidenib	Guideline	Actionable	Rezlidhia (olutasidenib) in combination with Vidaza (azacitidine) is included in guidelines (category 2B) for patients with higher-risk myelodysplastic syndrome harboring an IDH1 mutation (NCCN.org).	detail...
MSH6 negative	extrahepatic bile duct carcinoma	sensitive	Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab) is included in guidelines as primary therapy and subsequent-line therapy for patients with unresectable or metastatic biliary tract cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC), including extrahepatic cholangiocarcinoma (NCCN.org).	detail...
JAK2 rearrange	B-cell acute lymphoblastic leukemia	not applicable	N/A	Guideline	Prognostic	JAK2 rearrangements are associated with a poor prognosis in patients with B-cell acute lymphoblastic leukemia (NCCN.org).	detail...
NTRK1 fusion	breast cancer	sensitive	Repotrectinib	Guideline	Actionable	Augtyro (repotrectinib) is included in guidelines for patients with recurrent unresectable or stage IV (M1) breast cancer harboring an NTRK fusion (NCCN.org).	detail...
MLH1 negative	medullary thyroid carcinoma	sensitive	Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab) is included in guidelines for patients with medullary thyroid carcinoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) after progression on prior treatment (NCCN.org).	detail...
IDH2 mutant	high grade glioma	not applicable	N/A	Guideline	Diagnostic	IDH2 mutations aid in the diagnosis of gliomas (NCCN.org).	detail...
NTRK2 fusion	skin melanoma	sensitive	Larotrectinib	Guideline	Actionable	Vitrakvi (larotrectinib) therapy is included in guidelines for patients with metastatic or unresectable cutaneous melanoma harboring an NTRK fusion (NCCN.org).	detail...
VHL inact mut	hemangioblastoma	sensitive	Belzutifan	Guideline	Actionable	Welireg (belzutifan) is included in guidelines for patients with Von Hippel-Lindau disease-associated CNS hemangioblastoma that do not require immediate surgery (NCCN.org).	detail...
RET fusion	papillary thyroid carcinoma	sensitive	Selpercatinib	Guideline	Actionable	Retevmo (selpercatinib) is included in guidelines for patients with RAI-refractory papillary thyroid carcinoma harboring a RET fusion with progressive or symptomatic disease (NCCN.org).	detail...
NTRK2 fusion	follicular thyroid carcinoma	sensitive	Larotrectinib	Guideline	Actionable	Vitrakvi (larotrectinib) is included in guidelines for patients with RAI-refractory oncocytic thyroid carcinoma harboring an NTRK fusion with progressive or symptomatic disease (NCCN.org).	detail...
TP53 mutant	acute myeloid leukemia	not applicable	N/A	Guideline	Prognostic	TP53 mutations are associated with a poor/adverse prognosis in patients with non-APL acute myeloid leukemia (NCCN.org).	detail...
TP53 mutant	chronic lymphocytic leukemia/small lymphocytic lymphoma	sensitive	Alemtuzumab + Rituximab	Guideline	Actionable	Campath (alemtuzumab) combined with Rituxan (rituximab) is included in guidelines for patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma with a TP53 mutation after prior BTK inhibitor-based and BCL2 inhibitor-containing regimens (NCCN.org).	detail...
BRAF rearrange	pilocytic astrocytoma	sensitive	Tovorafenib	Guideline	Actionable	Ojemda (tovorafenib) is included in guidelines (category 2A) for patients with recurrent or progressive circumscribed glioma, including pilocytic astrocytoma, harboring BRAF fusions, rearrangements, or BRAF V600 mutations (NCCN.org).	detail...
NTRK1 fusion	intrahepatic cholangiocarcinoma	sensitive	Larotrectinib	Guideline	Actionable	Vitrakvi (larotrectinib) is included in guidelines as primary and subsequent-line therapy for patients with unresectable or metastatic biliary tract cancer harboring an NTRK fusion, including intrahepatic cholangiocarcinoma (NCCN.org).	detail...
NTRK1 fusion	cervical cancer	sensitive	Entrectinib	Guideline	Actionable	Rozlytrek (entrectinib) is included in guidelines as second-line or subsequent therapy (category 2A) for patients with recurrent or metastatic cervical cancer harboring an NTRK fusion (NCCN.org).	detail...
FGFR3 fusion	maxillary sinus cancer	sensitive	Erdafitinib	Guideline	Actionable	Balversa (erdafitinib) is included in guidelines as subsequent-line therapy (category 2B) for patients with maxillary sinus cancer harboring FGFR mutations or fusions and with no alternative options (NCCN.org).	detail...
MSH6 negative	rectum cancer	sensitive	Avelumab	Guideline	Actionable	Bavencio (avelumab) is included in guidelines (category 2A) for patients with advanced or metastatic rectal cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MSH6, MSH2, MLH1, or PMS2 expression by IHC) (NCCN.org).	detail...
BRAF V600E	lung non-small cell carcinoma	sensitive	Binimetinib + Encorafenib	Guideline	Actionable	Combination of Braftovi (encorafenib) and Mektovi (binimetinib) is included in guidelines as a first-line or subsequent therapy for advanced or metastatic non-small cell lung cancer patients harboring BRAF V600E mutations (NCCN.org).	detail...
NTRK1 fusion	oncocytic carcinoma of the thyroid	sensitive	Larotrectinib	Guideline	Actionable	Vitrakvi (larotrectinib) is included in guidelines for patients with RAI-refractory oncocytic thyroid carcinoma harboring an NTRK fusion with progressive or symptomatic disease (NCCN.org).	detail...
PDGFRB rearrange	chronic myelomonocytic leukemia	sensitive	Imatinib	Guideline	Actionable	Gleevec (imatinib) is included in guidelines for patients with chronic myelomonocytic leukemia harboring a PDGFRB rearrangement (NCCN.org).	detail...
RET fusion	stomach cancer	sensitive	Selpercatinib	Guideline	Actionable	Retevmo (selpercatinib) is included in guidelines as second-line or subsequent therapy for patients with unresectable locally advanced, recurrent, or metastatic gastric cancer harboring RET fusion (NCCN.org). (NCCN.org).	detail...
NTRK2 fusion	Erdheim-Chester disease	sensitive	Larotrectinib	Guideline	Actionable	Vitrakvi (larotrectinib) is included in guidelines as first-line or subsequent-line therapy for patients with Erdheim-Chester disease harboring NTRK2 fusions (NCCN.org).	detail...
NTRK2 fusion	cervical cancer	sensitive	Entrectinib	Guideline	Actionable	Rozlytrek (entrectinib) is included in guidelines as second-line or subsequent therapy (category 2A) for patients with recurrent or metastatic cervical cancer harboring an NTRK fusion (NCCN.org).	detail...
BRAF V600E	colon cancer	resistant	Panitumumab	Guideline	Actionable	Vectibix (panitumumab), as a monotherapy, is not indicated for use in colon cancer patients with BRAF V600E (NCCN.org).	detail...
MLH1 negative	gastroesophageal junction adenocarcinoma	sensitive	Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab) is included in guidelines as first-line, second-line, or subsequent therapy for patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) gastroesophageal junction cancer that are unresectable, locally advanced, recurrent, or metastatic (NCCN.org).	detail...
MSH6 negative	stomach cancer	sensitive	Ipilimumab + Nivolumab	Guideline	Actionable	Opdivo (nivolumab), in combination with Yervoy (ipilimumab), is included in guidelines as first-line, second-line, or subsequent therapy for patients with unresectable locally advanced, recurrent, or metastatic gastric cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
MLH1 negative	stomach cancer	sensitive	Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab) is included in guidelines as first-line, second-line, or subsequent therapy for patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) stomach cancer that are unresectable, locally advanced, recurrent, or metastatic (NCCN.org).	detail...
MSH6 negative	breast cancer	sensitive	Dostarlimab-gxly	Guideline	Actionable	Jemperli (dostarlimab-gxly) is included in guidelines for patients with recurrent unresectable or stage IV (M1) breast cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) who have progressed on or following prior treatment (NCCN.org).	detail...
IDH1 mutant	myelofibrosis	not applicable	N/A	Guideline	Prognostic	IDH1 mutations are associated with inferior leukemia-free survival in patients with myelofibrosis (NCCN.org).	detail...
FGFR1 fusion	supraglottis cancer	sensitive	Erdafitinib	Guideline	Actionable	Balversa (erdafitinib) is included in guidelines as subsequent-line therapy (category 2B) for patients with supraglottic larynx cancer harboring FGFR mutations or fusions and with no alternative options (NCCN.org).	detail...
FLT3 rearrange	myeloid neoplasm	sensitive	Gilteritinib	Guideline	Actionable	Xospata (gilteritinib) is included in guidelines for patients with a myeloid/lymphoid neoplasm with eosinophilia harboring a FLT3 rearrangement (NCCN.org).	detail...
NTRK2 fusion	low grade glioma	sensitive	Larotrectinib	Guideline	Actionable	Vitrakvi (larotrectinib) is included in guidelines for patients with recurrent or progressive low grade glioma harboring an NTRK fusion (NCCN.org).	detail...
NTRK1 fusion	Erdheim-Chester disease	sensitive	Repotrectinib	Guideline	Actionable	Augtyro (repotrectinib) is included in guidelines as first-line or subsequent-line therapy for patients with Erdheim-Chester disease harboring NTRK1 fusions (NCCN.org).	detail...
FLT3 rearrange	childhood B-cell acute lymphoblastic leukemia	not applicable	N/A	Guideline	Prognostic	FLT3 rearrangements are associated with a poor prognosis in pediatric patients with B-cell acute lymphoblastic leukemia (NCCN.org).	detail...
ROS1 fusion	skin melanoma	sensitive	Entrectinib	Guideline	Actionable	Rozlytrek (entrectinib) is included in guidelines as second-line therapy for metastatic or unresectable cutaneous melanoma patients with ROS1 fusions (NCCN.org).	detail...
MLH1 negative	prostate adenocarcinoma	sensitive	Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab) is included in guidelines as a second-line therapy for patients with advanced or metastatic prostate adenocarcinoma cancer with deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
RET fusion	medullary thyroid carcinoma	sensitive	Selpercatinib	Guideline	Actionable	Retevmo (selpercatinib) is included in guidelines as a preferred systemic therapy for patients with medullary thyroid carcinoma harboring pathogenic RET variants, including RET fusions (category 1) (NCCN.org).	detail...
NTRK2 fusion	high grade glioma	sensitive	Entrectinib	Guideline	Actionable	Rozlytrek (entrectinib) is included in guidelines as adjuvant therapy for pediatric patients with diffuse high-grade gliomas harboring NTRK fusions, or as a preferred regimen for patients with recurrent or progressive disease (NCCN.org).	detail...
TET2 mutant	myelofibrosis	not applicable	N/A	Guideline	Diagnostic	TET2 mutations aid in the diagnosis of primary myelofibrosis in the absence of JAK2, CALR, or MPL mutations (NCCN.org).	detail...
FLT3 exon17	acute myeloid leukemia	sensitive	Cytarabine + Midostaurin	Guideline	Actionable	Rydapt (midostaurin) in combination with Cytosar-U (cytarabine) is included in guidelines as consolidation therapy for patients with acute myeloid leukemia harboring a mutation in the FLT3 tyrosine kinase domain (exons 14-23) (NCCN.org).	detail...
TP53 loss	chronic lymphocytic leukemia/small lymphocytic lymphoma	sensitive	Duvelisib	Guideline	Actionable	Copiktra (duvelisib) is included in guidelines for patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma with TP53 loss after prior BTK inhibitor-based and BCL2 inhibitor-containing regimens (NCCN.org).	detail...
TP53 mutant	nephroblastoma	not applicable	N/A	Guideline	Risk Factor	Germline mutations in TP53 result in Li-Fraumeni syndrome, which is associated with increased risk of developing Wilms tumor (nephroblastoma) (NCCN.org).	detail...
NTRK2 fusion	follicular thyroid carcinoma	sensitive	Entrectinib	Guideline	Actionable	Rozlytrek (entrectinib) is included in guidelines for patients with RAI-refractory oncocytic thyroid carcinoma harboring an NTRK fusion with progressive or symptomatic disease (NCCN.org).	detail...
MLH1 negative	appendix adenocarcinoma	sensitive	Retifanlimab	Guideline	Actionable	Zynyz (retifanlimab) is included in guidelines (category 2A) for patients with advanced or metastatic appendiceal adenocarcinoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
MSH6 mutant	small intestine adenocarcinoma	not applicable	N/A	Guideline	Risk Factor	Lynch syndrome results from germline mutations in DNA mismatch repair genes including MLH1, MSH2, MSH6, and PMS2, and is associated with increased risk of developing small bowel adenocarcinoma (NCCN.org).	detail...
NTRK2 fusion	papillary thyroid carcinoma	sensitive	Larotrectinib	Guideline	Actionable	Vitrakvi (larotrectinib) is included in guidelines for patients with RAI-refractory papillary thyroid carcinoma harboring an NTRK fusion with progressive or symptomatic disease (NCCN.org).	detail...
ALK rearrange	high grade glioma	sensitive	Alectinib	Guideline	Actionable	Alecensa (alectinib) is included in guidelines as adjuvant therapy for pediatric patients with diffuse high-grade gliomas harboring ALK rearrangement, or as a preferred regimen for patients with recurrent or progressive disease (NCCN.org).	detail...
MSH6 negative	colon cancer	sensitive	Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab) is included in guidelines as preferred primary or subsequent therapy for patients with advanced or metastatic colon cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
MSH6 negative	pancreatic adenocarcinoma	sensitive	Dostarlimab-gxly	Guideline	Actionable	Jemperli (dostarlimab-gxly) is included in guidelines as subsequent therapy for patients with locally advanced, metastatic, or recurrent pancreatic adenocarcinoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) with good (ECOG 0-1), intermediate (ECOG 2) (category 2A), or poor (ECOG 3) (category 2B) performance status who have not received prior immunotherapy (NCCN.org).	detail...
ROS1 rearrange	lung non-small cell carcinoma	sensitive	Repotrectinib	Guideline	Actionable	Augtyro (repotrectinib) is included in guidelines as first-line or subsequent therapy for patients with advanced or metastatic ROS1-rearranged non-small cell lung cancer (NCCN.org).	detail...
FGFR2 act mut	glottis cancer	sensitive	Erdafitinib	Guideline	Actionable	Balversa (erdafitinib) is included in guidelines as subsequent-line therapy (category 2B) for patients with glottic larynx cancer harboring FGFR mutations or fusions and with no alternative options (NCCN.org).	detail...
NTRK2 fusion	anaplastic thyroid carcinoma	sensitive	Larotrectinib	Guideline	Actionable	Vitrakvi (larotrectinib) is included in guidelines as neoadjuvant treatment for anaplastic thyroid carcinoma patients harboring NTRK fusions with stage IVa or IVb borderline resectable disease, and as a preferred systemic therapy for those with metastatic disease (NCCN.org).	detail...
IDH1 act mut	oligodendroglioma	sensitive	Ivosidenib	Guideline	Actionable	Tibsovo (ivosidenib) is included in guidelines for patients with WHO grade 2 1p19q codeleted oligodendroglioma harboring an IDH1 activating mutation with residual/measurable disease or as adjuvant treatment after surgery/biopsy or recurrent or progressive disease and WHO grade 3 1p19q codeleted oligodendroglioma with recurrent or progressive disease or as adjuvant treatment (category 2B) (NCCN.org)	detail...
BRAF V600E	skin melanoma	sensitive	Cobimetinib + Vemurafenib	Guideline	Actionable	Zelboraf (vemurafenib) and Cotellic (cobimetinib) combination therapy is included in cutaneous melanoma guidelines for patients with metastatic or unresectable disease harboring a BRAF V600 activating mutation (NCCN.org).	detail...
TP53 mutant	mantle cell lymphoma	sensitive	Cyclophosphamide + Cytarabine + Dexamethasone + Doxorubicin + Prednisone + Rituximab + Vincristine Sulfate + Zanubrutinib	Guideline	Actionable	The combination of Brukinsa (zanubrutinib) plus RCHOP alternating with Rituxan (rituximab), Adexone (dexamethasone), Cytosar-U (cytarabine) plus a platinum is included in guidelines as induction therapy for patients with mantle cell lymphoma harboring a TP53 mutation (NCCN.org).	detail...
FLT3 exon 15 ins	acute myeloid leukemia	sensitive	Cytarabine + Quizartinib	Guideline	Actionable	Vanflyta (quizartinib) in combination with Cytosar-U (cytarabine) is included in guidelines as consolidation therapy for patients with acute myeloid leukemia harboring a FLT3 internal tandem duplication (FLT3-ITD) mutation (NCCN.org).	detail...
TP53 mutant	mantle cell lymphoma	sensitive	Cyclophosphamide + Cytarabine + Dexamethasone + Doxorubicin + Ibrutinib + Prednisone + Rituximab + Vincristine Sulfate	Guideline	Actionable	The combination of Imbruvica (ibrutinib) plus RCHOP alternating with Rituxan (rituximab), Adexone (dexamethasone), Cytosar-U (cytarabine) plus a platinum is included in guidelines as induction therapy for patients with mantle cell lymphoma harboring a TP53 mutation (NCCN.org).	detail...
MSH6 negative	esophagus squamous cell carcinoma	sensitive	Fluorouracil + Nivolumab + Oxaliplatin	Guideline	Actionable	Opdivo (nivolumab), in combination with Adrucil (fluorouracil) and Eloxatin (oxaliplatin) is included in guidelines as first-line therapy for patients with unresectable locally advanced, recurrent, or metastatic esophagus squamous cell carcinoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
NTRK2 fusion	Adenocarcinoma of Unknown Primary	sensitive	Entrectinib	Guideline	Actionable	Rozlytrek (entrectinib) is included in guidelines for patients with adenocarcinoma of unknown primary harboring NTRK2 fusions (NCCN.org).	detail...
NRAS wild-type	colon cancer	predicted - sensitive	Panitumumab	Guideline	Actionable	Vectibix (panitumumab), alone and in combination with chemotherapy, is included in guidelines for patients with advanced or metastatic colon cancer that is BRAF wild-type, KRAS wild-type, and NRAS wild-type (NCCN.org).	detail...
FLT3 exon22	acute myeloid leukemia	sensitive	Midostaurin	Guideline	Actionable	Rydapt (midostaurin) is included in guidelines as maintenance therapy for patients with acute myeloid leukemia harboring a mutation in the FLT3 tyrosine kinase domain (exons 14-23) (NCCN.org).	detail...
NTRK1 fusion	rectum cancer	sensitive	Larotrectinib	Guideline	Actionable	Vitrakvi (larotrectinib) is included in guidelines for advanced or metastatic rectal cancer patients with an NTRK fusion (NCCN.org).	detail...
RET fusion	Adenocarcinoma of Unknown Primary	sensitive	Selpercatinib	Guideline	Actionable	Retevmo (selpercatinib) is included in guidelines for patients with adenocarcinoma of unknown primary harboring RET fusions (NCCN.org).	detail...
MSH6 negative	appendix adenocarcinoma	sensitive	Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab) is included in guidelines (category 2A) for patients with advanced or metastatic appendiceal adenocarcinoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
BRAF V600E	colon cancer	sensitive	Capecitabine + Encorafenib + Oxaliplatin + Panitumumab	Guideline	Actionable	Braftovi (encorafenib) in combination with Vectibix (panitumumab) and CAPEOX is included in guidelines as an initial therapy (category 2A) for patients with advanced or metastatic colon cancer harboring BRAF V600E (NCCN.org).	detail...
RET fusion	pancreatic adenocarcinoma	sensitive	Selpercatinib	Guideline	Actionable	Retevmo (selpercatinib) is included in guidelines as first-line therapy for pancreatic adenocarcinoma patients harboring RET fusions with locally advanced or metastatic disease with good (ECOG 0-1) or intermediate (ECOG 2) performance status (PS), as first-line therapy for patients with metastatic diesease with poor PS (ECOG 3), and as subsequent therapy for patients with locally advanced, metastatic, or recurrent disease with good PS (NCCN.org).	detail...
PIK3CA mutant	Erdheim-Chester disease	sensitive	Sirolimus	Guideline	Actionable	Rapamune (sirolimus) is included in guidelines as first-line or subsequent-line therapy for patients with Erdheim-Chester disease harboring PIK3CA mutations (NCCN.org).	detail...
NTRK1 fusion	Squamous Cell Carcinoma of Unknown Primary	sensitive	Larotrectinib	Guideline	Actionable	Vitrakvi (larotrectinib) is included in guidelines for patients with squamous cell carcinoma of unknown primary harboring NTRK1 fusions (NCCN.org).	detail...
NRAS G12X	myelodysplastic syndrome	not applicable	N/A	Guideline	Prognostic	NRAS G12X is associated with a poor prognosis in patients with myelodysplastic syndrome (NCCN.org).	detail...
NTRK1 fusion	anaplastic astrocytoma	sensitive	Larotrectinib	Guideline	Actionable	Vitrakvi (larotrectinib) is included in guidelines for patients with recurrent anaplastic gliomas harboring an NTRK fusion, including anaplastic astrocytoma (NCCN.org).	detail...
RET mutant	medullary thyroid carcinoma	sensitive	Selpercatinib	Guideline	Actionable	Retevmo (selpercatinib) is included in guidelines as a preferred systemic therapy for patients with medullary thyroid carcinoma harboring pathogenic RET variants (category 1) (NCCN.org).	detail...
RET mutant	medullary thyroid carcinoma	sensitive	Pralsetinib	Guideline	Actionable	Gavreto (pralsetinib) is included in guidelines as a preferred systemic therapy for patients with medullary thyroid carcinoma harboring pathogenic RET variants (category 2B) (NCCN.org).	detail...
IDH2 mutant	myelofibrosis	not applicable	N/A	Guideline	Diagnostic	IDH2 mutations aid in the diagnosis of primary myelofibrosis in the absence of JAK2, CALR, or MPL mutations (NCCN.org).	detail...
FGFR1 act mut	lung non-small cell carcinoma	sensitive	Erdafitinib	Guideline	Actionable	Balversa (erdafitinib) is included in guidelines for patients with metastatic non-small cell lung cancer harboring oncogenic or likely oncogenic FGFR alterations (NCCN.org).	detail...
NTRK2 fusion	low grade glioma	sensitive	Entrectinib	Guideline	Actionable	Rozlytrek (entrectinib) is included in guidelines for patients with recurrent or progressive low grade glioma harboring an NTRK fusion (NCCN.org).	detail...
FGFR2 fusion	supraglottis cancer	sensitive	Erdafitinib	Guideline	Actionable	Balversa (erdafitinib) is included in guidelines as subsequent-line therapy (category 2B) for patients with supraglottic larynx cancer harboring FGFR mutations or fusions and with no alternative options (NCCN.org).	detail...
TET2 mutant	angioimmunoblastic T-cell lymphoma	not applicable	N/A	Guideline	Diagnostic	TET2 mutations aid in the diagnosis of angioimmunoblastic T-cell lymphoma (NCCN.org).	detail...
MLH1 negative	oncocytic carcinoma of the thyroid	sensitive	Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab) is included in guidelines for patients with Hurthle cell thyroid carcinoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) after progression on prior treatment (NCCN.org).	detail...
MSH6 negative	colon cancer	sensitive	Dostarlimab-gxly	Guideline	Actionable	Jemperli (dostarlimab-gxly) is included in guidelines as subsequent therapy for patients with advanced or metastatic colon cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
JAK2 mutant	B-cell acute lymphoblastic leukemia	not applicable	N/A	Guideline	Prognostic	JAK2 mutations are associated with a poor prognosis in patients with B-cell acute lymphoblastic leukemia (NCCN.org).	detail...
RET fusion	papillary thyroid carcinoma	sensitive	Pralsetinib	Guideline	Actionable	Gavreto (pralsetinib) is included in guidelines for patients with RAI-refractory papillary thyroid carcinoma harboring a RET fusion with progressive or symptomatic disease (NCCN.org).	detail...
ALK rearrange	high grade glioma	sensitive	Lorlatinib	Guideline	Actionable	Lorbrena (lorlatinib) is included in guidelines as adjuvant therapy for pediatric patients with diffuse high-grade gliomas harboring ALK rearrangement, or as a preferred regimen for patients with recurrent or progressive disease (NCCN.org).	detail...
TP53 mutant	chronic lymphocytic leukemia/small lymphocytic lymphoma	predicted - sensitive	Zanubrutinib	Guideline	Actionable	Brukinsa (zanubrutinib) is included in guidelines as first-line therapy (category 2A) and second line therapy or subsequent therapy (category 1) for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with a TP53 mutation (NCCN.org).	detail...
TP53 loss	chronic lymphocytic leukemia/small lymphocytic lymphoma	sensitive	Obinutuzumab + Venetoclax	Guideline	Actionable	The combination of Venclexta (venetoclax) and Gazyva (obinutuzumab) is included in guidelines as first-line therapy for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with TP53 loss (NCCN.org).	detail...
NTRK1 fusion	vulva squamous cell carcinoma	sensitive	Entrectinib	Guideline	Actionable	Rozlytrek (entrectinib) is included in guidelines as a second-line or subsequent therapy for patients with advanced or recurrent/metastatic vulvar squamous cell carcinoma harboring an NTRK fusion (NCCN.org).	detail...
MSH6 negative	ovary epithelial cancer	sensitive	Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab) is included in guidelines as systemic therapy for patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
FLT3 exon18	acute myeloid leukemia	sensitive	Cytarabine + Midostaurin	Guideline	Actionable	Rydapt (midostaurin) in combination with Cytosar-U (cytarabine) is included in guidelines as consolidation therapy for patients with acute myeloid leukemia harboring a mutation in the FLT3 tyrosine kinase domain (exons 14-23) (NCCN.org).	detail...
IDH2 mutant	acute myeloid leukemia	sensitive	Cytarabine + Venetoclax	Guideline	Actionable	Venclexta (venetoclax) in combination with Cytosar-U (cytarabine) is included in guidelines for adult patients with acute myeloid leukemia harboring an IDH2 mutation (NCCN.org).	detail...
NTRK1 fusion	high grade glioma	sensitive	Larotrectinib	Guideline	Actionable	Vitrakvi (larotrectinib) is included in guidelines as adjuvant therapy for pediatric patients with diffuse high-grade gliomas harboring NTRK fusions, or as a preferred regimen for patients with recurrent or progressive disease (NCCN.org).	detail...
FGFR2 act mut	oropharynx cancer	sensitive	Erdafitinib	Guideline	Actionable	Balversa (erdafitinib) is included in guidelines as subsequent-line therapy (category 2B) for patients with oropharynx cancer harboring FGFR mutations or fusions and with no alternative options (NCCN.org).	detail...
NTRK2 fusion	extrahepatic bile duct carcinoma	sensitive	Repotrectinib	Guideline	Actionable	Augtyro (repotrectinib) is included in guidelines as primary and subsequent-line therapy (category 2A) for patients with unresectable or metastatic biliary tract cancer harboring NTRK fusions, including extrahepatic cholangiocarcinoma (NCCN.org).	detail...
BRAF V600E	skin melanoma	sensitive	Atezolizumab + Cobimetinib + Vemurafenib	Guideline	Actionable	Zelboraf (vemurafenib) plus Cotellic (cobimetinib) in combination with an immune checkpoint inhibitor, such as Tecentriq (atezolizumab), is included in guidelines as second-line or subsequent therapy (category 2A) for patients with metastatic or unresectable cutaneous melanoma harboring a BRAF V600 mutation, such as BRAF V600E (NCCN.org).	detail...
MLH1 negative	penile cancer	sensitive	Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab) is included in guidelines as subsequent-line systemic therapy for metastatic/recurrent penile cancer patients with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
NTRK2 fusion	subependymal giant cell astrocytoma	sensitive	Repotrectinib	Guideline	Actionable	Augtyro (repotrectinib) is included in guidelines (category 2B) for patients with recurrent or progressive circumscribed glioma, including subependymal giant cell astrocytoma, harboring an NTRK fusion (NCCN.org).	detail...
MSH6 negative	rectum cancer	sensitive	Tislelizumab	Guideline	Actionable	Tevimbra (tislelizumab) is included in guidelines (category 2A) for patients with advanced or metastatic rectal cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, MSH2, PMS2, or MSH6 expression by IHC) (NCCN.org).	detail...
NTRK1 fusion	gallbladder cancer	sensitive	Larotrectinib	Guideline	Actionable	Vitrakvi (larotrectinib) is included in guidelines as primary and subsequent-line therapy for patients with unresectable or metastatic biliary tract cancer harboring an NTRK fusion, including gallbladder cancer (NCCN.org).	detail...
JAK2 exon12	polycythemia vera	not applicable	N/A	Guideline	Diagnostic	JAK2 exon 12 mutations aid in the diagnosis of polycythemia vera (NCCN.org).	detail...
NTRK1 fusion	hepatocellular carcinoma	sensitive	Entrectinib	Guideline	Actionable	Rozlytrek (entrectinib) is included in guidelines as subsequent-line therapy for patients with hepatocellular carcinoma harboring an NTRK fusion (NCCN.org).	detail...
NTRK1 fusion	soft tissue sarcoma	sensitive	Entrectinib	Guideline	Actionable	Rozlytrek (entrectinib) is in guidelines for patients with soft tissue sarcoma harboring an NTRK fusion (NCCN.org).	detail...
BRAF V600E	glioblastoma	sensitive	Cobimetinib + Vemurafenib	Guideline	Actionable	Combination of Zelboraf (vemurafenib) and Cotellic (cobimetinib) is included in guidelines for patients with recurrent glioblastoma harboring BRAF V600E (NCCN.org).	detail...
NTRK1 fusion	rectum cancer	sensitive	Repotrectinib	Guideline	Actionable	Augtyro (repotrectinib) is included in guidelines as second-line or subsequent therapy (category 2A) for patients with advanced or metastatic rectal cancer harboring an NTRK fusion (NCCN.org).	detail...
FGFR2 rearrange	cholangiocarcinoma	sensitive	Pemigatinib	Guideline	Actionable	Pemazyre (pemigatinib) is included in guidelines as subsequent-line therapy for patients with cholangiocarcinoma harboring FGFR2 fusions or rearrangements (NCCN.org).	detail...
NTRK2 fusion	pancreatic adenocarcinoma	sensitive	Repotrectinib	Guideline	Actionable	Augtyro (repotrectinib) is included in guidelines as first-line therapy for pancreatic adenocarcinoma patients harboring an NTRK fusion with locally advanced disease with good (ECOG 0-1) or intermediate (ECOG 2) performance status (PS), or with metastatic disease with good, intermediate (category 2A), or poor (ECOG 3) (category 2B) PS, and as subsequent therapy for patients with locally advanced, metastatic, or recurrent disease with good (category 2A), intermediate, or poor (category 2B) PS (NCCN.org).	detail...
MLH1 inact mut	prostate cancer	sensitive	Enzalutamide + Talazoparib	Guideline	Actionable	Talzenna (talazoparib) plus Xtandi (enzalutamide) is included in guidelines as systemic therapy for patients with metastatic castration-resistant prostate cancer harboring a pathogenic germline or somatic MLH1 mutation who have not been treated in the setting of castration-resistant prostate cancer (NCCN.org).	detail...
NRAS mutant	skin melanoma	sensitive	Binimetinib	Guideline	Actionable	Mektovi (binimetinib) is included in guidelines as second-line therapy for patients with metastatic or unresectable cutaneous melanoma harboring an NRAS mutation (NCCN.org).	detail...
NTRK1 fusion	endometrial carcinoma	sensitive	Larotrectinib	Guideline	Actionable	Vitrakvi (larotrectinib) is included in guidelines as a second-line or subsequent-line therapy (category 2A) for patients with recurrent endometrial carcinoma harboring an NTRK fusion (NCCN.org).	detail...
IDH1 mutant	acute myeloid leukemia	sensitive	Ivosidenib	Guideline	Actionable	Tibsovo (ivosidenib) is included in guidelines for patients with relapsed or refractory acute myeloid leukemia harboring an IDH1 mutation (NCCN.org).	detail...
TP53 loss	chronic lymphocytic leukemia/small lymphocytic lymphoma	sensitive	Methylprednisolone + Rituximab	Guideline	Actionable	Artisone-Wyeth (methylprednisolone) combined with Rituxan (rituximab) is included in guidelines as first-line therapy for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with TP53 loss and for patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma with TP53 loss after prior BTK inhibitor-based and BCL2 inhibitor-containing regimens (NCCN.org).	detail...
JAK2 rearrange	myeloid neoplasm	sensitive	Ruxolitinib	Guideline	Actionable	Jakafi (ruxolitinib) is included in guidelines for patients with a myeloid/lymphoid neoplasm with eosinophilia harboring a JAK2 rearrangement (NCCN.org).	detail...
BRAF V600E	stomach cancer	sensitive	Dabrafenib + Trametinib	Guideline	Actionable	Tafinlar (dabrafenib) and Mekinist (trametinib) combination therapy is included in guidelines as second-line or subsequent therapy for patients with unresectable locally advanced, recurrent, or metastatic gastric cancer harboring BRAF V600E (NCCN.org).	detail...
MLH1 negative	appendix adenocarcinoma	sensitive	Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab) is included in guidelines (category 2A) for patients with advanced or metastatic appendiceal adenocarcinoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
MSH6 mutant	pancreatic cancer	not applicable	N/A	Guideline	Risk Factor	Germline mutations in MSH6 result in Lynch syndrome, which is associated with increased risk of developing pancreatic cancer (NCCN.org).	detail...
TP53 mutant	osteosarcoma	not applicable	N/A	Guideline	Risk Factor	Germline mutations in TP53 result in Li-Fraumeni syndrome, which is associated with increased risk of developing osteosarcoma (NCCN.org).	detail...
MLH1 negative	colon cancer	sensitive	Dostarlimab-gxly	Guideline	Actionable	Jemperli (dostarlimab-gxly) is included in guidelines as subsequent therapy for patients with advanced or metastatic colon cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
FGFR2 act mut	salivary gland cancer	sensitive	Erdafitinib	Guideline	Actionable	Balversa (erdafitinib) is included in guidelines for patients with unresectable locally advanced, recurrent, or metastatic salivary gland tumors harboring FGFR mutations or fusions (category 2B) who received prior systemic therapy and have no alternative systemic therapy available (NCCN.org).	detail...
MLH1 negative	small intestine adenocarcinoma	sensitive	Nivolumab	Guideline	Actionable	Opdivo (nivolumab) is included in guidelines as systemic therapy (category 2A) for patients with advanced or metastatic small bowel adenocarcinoma with deficient mismatch repair (dMMR, often defined by the loss of MLH1, MSH2, MSH6, or PMS2 expression by IHC) (NCCN.org).	detail...
MSH6 negative	colon cancer	sensitive	Penpulimab-kcqx	Guideline	Actionable	Penpulimab-kcqx (AK105) is included in guidelines (category 2A) for patients with advanced or metastatic colon cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MSH6, MSH2, MLH1, or PMS2 expression by IHC) (NCCN.org).	detail...
NTRK2 fusion	pancreatic adenocarcinoma	sensitive	Larotrectinib	Guideline	Actionable	Vitrakvi (larotrectinib) is included in guidelines as first-line therapy for pancreatic adenocarcinoma patients harboring an NTRK fusion with locally advanced disease with good (ECOG 0-1) or intermediate (ECOG 2) performance status (PS), as first-line therapy for patients with metastatic disease with good, intermediate, or poor (ECOG 3) PS, as subsequent therapy for patients with locally advanced, metastatic, or recurrent disease with good, intermediate, or poor PS (NCCN.org).	detail...
ALK rearrange	inflammatory myofibroblastic tumor	sensitive	Brigatinib	Guideline	Actionable	Alunbrig (brigatinib) is included in guidelines as first-line therapy for patients with advanced, recurrent, metastatic, or inoperable inflammatory myofibroblastic tumor harboring ALK translocations (NCCN.org).	detail...
NTRK1 fusion	pancreatic adenocarcinoma	sensitive	Repotrectinib	Guideline	Actionable	Augtyro (repotrectinib) is included in guidelines as first-line therapy for pancreatic adenocarcinoma patients harboring an NTRK fusion with locally advanced disease with good (ECOG 0-1) or intermediate (ECOG 2) performance status (PS), or with metastatic disease with good, intermediate (category 2A), or poor (ECOG 3) (category 2B) PS, and as subsequent therapy for patients with locally advanced, metastatic, or recurrent disease with good (category 2A), intermediate, or poor (category 2B) PS (NCCN.org).	detail...
IDH1 mutant	high grade glioma	not applicable	N/A	Guideline	Diagnostic	IDH1 mutations aid in the diagnosis of gliomas (PMID: 23041832, PMID: 19755387, PMID: 19915484; NCCN.org).	detail... 23041832 19755387 19915484
KMT2A rearrange	B-cell acute lymphoblastic leukemia	not applicable	N/A	Guideline	Prognostic	KMT2A rearrangements are associated with a poor prognosis in patients with B-cell acute lymphoblastic leukemia (NCCN.org).	detail...
ALK rearrange	anaplastic large cell lymphoma	sensitive	Brigatinib	Guideline	Actionable	Alunbrig (brigatinib) is included in guidelines as initial, second-line, and subsequent therapy for patients with anaplastic large cell lymphoma harboring ALK rearrangements (NCCN.org).	detail...
FGFR3 act mut	salivary gland cancer	sensitive	Erdafitinib	Guideline	Actionable	Balversa (erdafitinib) is included in guidelines for patients with unresectable locally advanced, recurrent, or metastatic salivary gland tumors harboring FGFR mutations or fusions (category 2B) who received prior systemic therapy and have no alternative systemic therapy available (NCCN.org).	detail...
TP53 mutant	chronic lymphocytic leukemia/small lymphocytic lymphoma	sensitive	Idelalisib + Rituximab	Guideline	Actionable	Zydelig (idelalisib) combined with Rituxan (rituximab) is included in guidelines for patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma with a TP53 mutation after prior BTK inhibitor-based and BCL2 inhibitor-containing regimens (NCCN.org).	detail...
BRAF fusion	pilocytic astrocytoma	not applicable	N/A	Guideline	Prognostic	BRAF fusions are associated with indolent disease in patients with pilocytic astrocytoma (NCCN.org).	detail...
FGFR1 act mut	hypopharynx cancer	sensitive	Erdafitinib	Guideline	Actionable	Balversa (erdafitinib) is included in guidelines as subsequent-line therapy (category 2B) for patients with hypopharynx cancer harboring FGFR mutations or fusions and with no alternative options (NCCN.org).	detail...
MLH1 negative	glottis cancer	sensitive	Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab) is included in guidelines as first- and subsequent-line therapy for patients with mismatch repair deficient (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) recurrent, unresectable, or metastatic glottic larynx cancer (NCCN.org).	detail...
TP53 mutant	chronic lymphocytic leukemia/small lymphocytic lymphoma	sensitive	Obinutuzumab	Guideline	Actionable	Gazyva (obinutuzumab) is included in guidelines as first-line therapy for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with a TP53 mutation (NCCN.org).	detail...
MLH1 mutant	colon cancer	not applicable	N/A	Guideline	Risk Factor	Lynch syndrome results from germline mutations in DNA mismatch repair genes including MLH1, MSH2, MSH6, and PMS2, and is associated with increased risk of developing colon cancer (NCCN.org).	detail...
BRAF V600E	intrahepatic cholangiocarcinoma	sensitive	Dabrafenib + Trametinib	Guideline	Actionable	Tafinlar (dabrafenib) in combination with Mekinist (trametinib) is included in guidelines as subsequent-line therapy for patients with biliary cancer harboring BRAF V600E, including intrahepatic cholangiocarcinoma (NCCN.org).	detail...
MLH1 negative	esophagus adenocarcinoma	sensitive	Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab) is included in guidelines as first-line, second-line, or subsequent therapy for patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) esophageal adenocarcinoma that are unresectable, locally advanced, recurrent, or metastatic (NCCN.org).	detail...
NTRK1 fusion	gallbladder cancer	sensitive	Entrectinib	Guideline	Actionable	Rozlytrek (entrectinib) is included in guidelines as primary and subsequent-line therapy for patients with unresectable or metastatic biliary tract cancer harboring an NTRK fusion, including gallbladder cancer (NCCN.org).	detail...
IDH2 wild-type	high grade glioma	not applicable	N/A	Guideline	Risk Factor	IDH2 wild-type is associated with increased risk of aggressive disease in patients with grade II or III infiltrative gliomas (NCCN.org).	detail...
KIT act mut	gastrointestinal stromal tumor	not applicable	N/A	Guideline	Diagnostic	KIT activating mutations aid the diagnosis of gastrointestinal stromal tumor (NCCN.org).	detail...
TP53 mutant	chronic lymphocytic leukemia/small lymphocytic lymphoma	sensitive	Acalabrutinib	Guideline	Actionable	Calquence (acalabrutinib) is included in guidelines as first-line (category 2A) and second-line or subsequent therapy (category 1) for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with a TP53 mutation (NCCN.org).	detail...
NTRK2 fusion	vulva squamous cell carcinoma	sensitive	Entrectinib	Guideline	Actionable	Rozlytrek (entrectinib) is included in guidelines as a second-line or subsequent therapy for patients with advanced or recurrent/metastatic vulvar squamous cell carcinoma harboring an NTRK fusion (NCCN.org).	detail...
RET fusion	Squamous Cell Carcinoma of Unknown Primary	sensitive	Selpercatinib	Guideline	Actionable	Retevmo (selpercatinib) is included in guidelines (category 2B) for patients with squamous cell carcinoma of unknown primary harboring RET fusions (NCCN.org).	detail...
IDH1 mutant	acute myeloid leukemia	sensitive	Azacitidine + Ivosidenib	Guideline	Actionable	Tibsovo (ivosidenib) in combination with Vidaza (azacitidine) is included in guidelines (category 1) for patients with relapsed or refractory acute myeloid leukemia harboring an IDH1 mutation (NCCN.org).	detail...
NTRK2 fusion	uterine corpus sarcoma	sensitive	Entrectinib	Guideline	Actionable	Rozlytrek (entrectinib) is included in guidelines as first-line therapy for patients with advanced, recurrent, metastatic, or inoperable uterine sarcoma harboring an NTRK fusion (NCCN.org).	detail...
BRAF V600K	skin melanoma	sensitive	Atezolizumab + Cobimetinib + Vemurafenib	Guideline	Actionable	Zelboraf (vemurafenib) plus Cotellic (cobimetinib) in combination with an immune checkpoint inhibitor, such as Tecentriq (atezolizumab), is included in guidelines as second-line or subsequent therapy (category 2A) for patients with metastatic or unresectable cutaneous melanoma harboring a BRAF V600 mutation, such as BRAF V600K (NCCN.org).	detail...
MSH6 negative	ampulla of Vater adenocarcinoma	sensitive	Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab) is included in guidelines as first-line or subsequent therapy for metastatic ampullary adenocarcinoma patients with deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
BRAF wild-type	colon cancer	predicted - sensitive	Panitumumab	Guideline	Actionable	Vectibix (panitumumab), alone and in combination with chemotherapy, is included in guidelines for patients with advanced or metastatic colon cancer that is BRAF wild-type, KRAS wild-type, and NRAS wild-type (NCCN.org).	detail...
MLH1 negative	small intestine adenocarcinoma	sensitive	Tislelizumab	Guideline	Actionable	Tevimbra (tislelizumab) is included in guidelines as systemic therapy (category 2A) for patients with advanced or metastatic small bowel adenocarcinoma with deficient mismatch repair (dMMR, often defined by the loss of MLH1, MSH2, MSH6, or PMS2 expression by IHC) (NCCN.org).	detail...
IDH1 mutant	acute myeloid leukemia	sensitive	Decitabine + Venetoclax	Guideline	Actionable	Venclexta (venetoclax) in combination with Dacogen (decitabine) is included in guidelines for adult patients with acute myeloid leukemia harboring an IDH1 mutation (NCCN.org).	detail...
MLH1 negative	intrahepatic cholangiocarcinoma	sensitive	Dostarlimab-gxly	Guideline	Actionable	Jemperli (dostarlimab-gxly) is included in guidelines as subsequent therapy (category 2B) for patients with biliary tract cancer with deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC), including intrahepatic cholangiocarcinoma (NCCN.org).	detail...
FLT3 exon20	acute myeloid leukemia	sensitive	Midostaurin	Guideline	Actionable	Rydapt (midostaurin) is included in guidelines as maintenance therapy for patients with acute myeloid leukemia harboring a mutation in the FLT3 tyrosine kinase domain (exons 14-23) (NCCN.org).	detail...
RET fusion	Erdheim-Chester disease	sensitive	Selpercatinib	Guideline	Actionable	Retevmo (selpercatinib) is included in guidelines as first-line or subsequent-line therapy for patients with Erdheim-Chester disease harboring RET fusions (NCCN.org).	detail...
MLH1 negative	appendix adenocarcinoma	sensitive	Cemiplimab	Guideline	Actionable	Libtayo (cemiplimab) is included in guidelines (category 2A) for patients with advanced or metastatic appendiceal adenocarcinoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
MSH6 mutant	stomach cancer	not applicable	N/A	Guideline	Risk Factor	Germline mutations in MSH6 result in Lynch syndrome, which is associated with increased risk of developing pancreatic cancer (NCCN.org).	detail...
MLH1 negative	soft tissue sarcoma	sensitive	Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab) is included in guidelines as systemic therapy for soft tissue sarcoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC), regardless of sarcoma sub-type (NCCN.org).	detail...
IDH1 mutant	angioimmunoblastic T-cell lymphoma	not applicable	N/A	Guideline	Diagnostic	IDH1 mutations aid in the diagnosis of angioimmunoblastic T-cell lymphoma (NCCN.org).	detail...
BRAF V600E	ampulla of Vater adenocarcinoma	sensitive	Dabrafenib + Trametinib	Guideline	Actionable	Tafinlar (dabrafenib) and Mekinist (trametinib) combination therapy is included in guidelines as first-line therapy with good (ECOG 0-1; category 3) or poor (category 2B) performance status, or as subsequent therapy (category 2A), for metastatic ampullary adenocarcinoma patients harboring BRAF V600E (NCCN.org).	detail...
NTRK1 fusion	neuroendocrine tumor	sensitive	Larotrectinib	Guideline	Actionable	Vitrakvi (larotrectinib) is included in guidelines for patients with unresectable or metastatic extrapulmonary poorly differentiated neuroendocrine carcinoma, large or small cell carcinoma, or mixed neuroendocrine/non-neuroendocrine neoplasms harboring an NTRK fusion who have progressed on or following prior treatment (NCCN.org).	detail...
MLH1 negative	ampulla of Vater adenocarcinoma	sensitive	Nivolumab	Guideline	Actionable	Opdivo (nivolumab) is included in guidelines as first-line therapy (category 2A) for metastatic ampullary adenocarcinoma patients with deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) and poor (ECOG 3) performance status, and as subsequent therapy (category 2A) for patients with intermediate (ECOG 2) or poor (ECOG 3) performance status (NCCN.org).	detail...
BRAF V600K	skin melanoma	sensitive	Dabrafenib + Pembrolizumab + Trametinib	Guideline	Actionable	Tafinlar (dabrafenib) plus Mekinist (trametinib) in combination with an immune checkpoint inhibitor, such as Keytruda (pembrolizumab), is included in guidelines as second-line or subsequent therapy (category 2A) for patients with metastatic or unresectable cutaneous melanoma harboring a BRAF V600 mutation, such as BRAF V600K (NCCN.org).	detail...
BRAF V600E	rectum cancer	resistant	Cetuximab	Guideline	Actionable	Erbitux (cetuximab), as a monotherapy, is not indicated for use in rectum cancer patients with BRAF V600E (NCCN.org).	detail...
BRAF V600E	pilocytic astrocytoma	sensitive	Dabrafenib + Trametinib	Guideline	Actionable	Combination of Mekinist (trametinib) and Tafinlar (dabrafenib) is included in guidelines as an adjuvant treatment for patients with pilocytic astrocytoma harboring BRAF V600E (NCCN.org).	detail...
RET fusion	cervical cancer	sensitive	Selpercatinib	Guideline	Actionable	Retevmo (selpercatinib) is included in guidelines as second-line or subsequent therapy (category 2A) for patients with recurrent or metastatic cervical cancer harboring a RET fusion (NCCN.org).	detail...
FLT3 exon 15 ins	acute myeloid leukemia	sensitive	Azacitidine + Sorafenib	Guideline	Actionable	Nexavar (sorafenib) in combination with Vidaza (azacitidine) is included in guidelines for patients with relapsed or refractory acute myeloid leukemia harboring a FLT3 internal tandem duplication (FLT3-ITD) mutation (NCCN.org).	detail...
FGFR1 fusion	maxillary sinus cancer	sensitive	Erdafitinib	Guideline	Actionable	Balversa (erdafitinib) is included in guidelines as subsequent-line therapy (category 2B) for patients with maxillary sinus cancer harboring FGFR mutations or fusions and with no alternative options (NCCN.org).	detail...
TP53 loss	chronic lymphocytic leukemia/small lymphocytic lymphoma	sensitive	Methylprednisolone + Obinutuzumab	Guideline	Actionable	Artisone-Wyeth (methylprednisolone) combined with Gazyva (obinutuzumab) is included in guidelines as first-line therapy for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with TP53 loss and for patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma with TP53 loss after prior BTK inhibitor-based and BCL2 inhibitor-containing regimens (NCCN.org).	detail...
RET fusion	intrahepatic cholangiocarcinoma	sensitive	Pralsetinib	Guideline	Actionable	Gavreto (pralsetinib) is included in guidelines as primary (category 2B) and subsequent-line therapy (category 2B) for patients with unresectable or metastatic biliary tract cancer harboring RET fusions, including intrahepatic cholangiocarcinoma (NCCN.org).	detail...
FGFR2 rearrange	cholangiocarcinoma	sensitive	Erdafitinib	Guideline	Actionable	Balversa (erdafitinib) is included in guidelines as subsequent-line therapy for patients with cholangiocarcinoma harboring FGFR2 fusions or rearrangements (NCCN.org).	detail...
FLT3 exon19	acute myeloid leukemia	sensitive	Cytarabine + Midostaurin	Guideline	Actionable	Rydapt (midostaurin) in combination with Cytosar-U (cytarabine) is included in guidelines as consolidation therapy for patients with acute myeloid leukemia harboring a mutation in the FLT3 tyrosine kinase domain (exons 14-23) (NCCN.org).	detail...
FGFR3 fusion	hypopharynx cancer	sensitive	Erdafitinib	Guideline	Actionable	Balversa (erdafitinib) is included in guidelines as subsequent-line therapy (category 2B) for patients with hypopharynx cancer harboring FGFR mutations or fusions and with no alternative options (NCCN.org).	detail...
BRAF V600K	skin melanoma	sensitive	Cobimetinib + Vemurafenib	Guideline	Actionable	Zelboraf (vemurafenib) and Cotellic (cobimetinib) combination therapy is included in cutaneous melanoma guidelines for patients with metastatic or unresectable disease harboring a BRAF V600 activating mutation (NCCN.org).	detail...
NTRK1 fusion	gallbladder cancer	sensitive	Repotrectinib	Guideline	Actionable	Augtyro (repotrectinib) is included in guidelines as primary and subsequent-line therapy (category 2A) for patients with unresectable or metastatic biliary tract cancer harboring NTRK fusions, including gallbladder cancer (NCCN.org).	detail...
BRAF V600E	colon cancer	sensitive	Cetuximab + Encorafenib	Guideline	Actionable	Braftovi (encorafenib) in combination with Erbitux (cetuximab) is included in guidelines (category 2A) as primary or subsequent therapy for patients with colon cancer harboring BRAF V600E (NCCN.org).	detail...
KIT exon9	gastrointestinal stromal tumor	sensitive	Imatinib	Guideline	Actionable	Gleevec (imatinib) is included in guidelines for patients with gastrointestinal stromal tumor (GIST) harboring KIT exon 9 mutations (NCCN.org).	detail...
FLT3 rearrange	B-cell acute lymphoblastic leukemia	not applicable	N/A	Guideline	Prognostic	FLT3 rearrangements are associated with a poor prognosis in patients with B-cell acute lymphoblastic leukemia (NCCN.org).	detail...
NTRK2 fusion	gastrointestinal stromal tumor	sensitive	Repotrectinib	Guideline	Actionable	Augtyro (repotrectinib) is included in guidelines as neoadjuvant therapy (category 2B) for patients with resectable disease and as first-line or second-line systemic therapy (category 2A) for patients with unresectable or metastatic gastrointestinal stromal tumor (GIST) harboring NTRK fusions (NCCN.org).	detail...
FLT3 rearrange	myeloid neoplasm	sensitive	Quizartinib	Guideline	Actionable	Vanflyta (quizartinib) is included in guidelines for patients with a myeloid/lymphoid neoplasm with eosinophilia harboring a FLT3 rearrangement (NCCN.org).	detail...
BRAF V600E	hairy cell leukemia	not applicable	N/A	Guideline	Diagnostic	BRAF V600E is diagnostic and aids in distinguishing classic hairy cell leukemia (cHCL) from variant hairy cell leukemia (HCLv) and other B-cell lymphomas and leukemias (PMID: 29118233, NCCN.org).	detail... 29118233
BRAF V600E	small intestine adenocarcinoma	sensitive	Cetuximab + Encorafenib	Guideline	Actionable	Braftovi (encorafenib) in combination with Erbitux (cetuximab) is included in guidelines as second-line or subsequent therapy (category 2A) for patients with advanced or metastatic small bowel adenocarcinoma harboring BRAF V600E (NCCN.org).	detail...
NTRK1 fusion	ampulla of Vater adenocarcinoma	sensitive	Repotrectinib	Guideline	Actionable	Augtyro (repotrectinib) is included in guidelines as first-line or subsequent therapy for patients with metastatic ampullary adenocarcinoma harboring NTRK fusions (NCCN.org).	detail...
RET rearrange	lung non-small cell carcinoma	sensitive	Pralsetinib	Guideline	Actionable	Gavreto (pralsetinib) is included in guidelines as a first-line therapy for patients with advanced or metastatic non-small cell lung cancer harboring RET rearrangements (NCCN.org).	detail...
FGFR1 rearrange	childhood B-cell acute lymphoblastic leukemia	not applicable	N/A	Guideline	Prognostic	FGFR1 rearrangements are associated with a poor prognosis in pediatric patients with B-cell acute lymphoblastic leukemia (NCCN.org).	detail...
MLH1 negative	colon cancer	sensitive	Atezolizumab + Capecitabine + Oxaliplatin	Guideline	Actionable	Tecentriq (atezolizumab) in combination with Xeloda (capecitabine) and Eloxatin (oxaliplatin) is included in guidelines as adjuvant therapy for patients with colon cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
MLH1 negative	small intestine adenocarcinoma	sensitive	Cemiplimab	Guideline	Actionable	Libtayo (cemiplimab) is included in guidelines as systemic therapy (category 2A) for patients with advanced or metastatic small bowel adenocarcinoma with deficient mismatch repair (dMMR, often defined by the loss of MLH1, MSH2, MSH6, or PMS2 expression by IHC) (NCCN.org).	detail...
NTRK2 fusion	intrahepatic cholangiocarcinoma	sensitive	Larotrectinib	Guideline	Actionable	Vitrakvi (larotrectinib) is included in guidelines as primary and subsequent-line therapy for patients with unresectable or metastatic biliary tract cancer harboring an NTRK fusion, including intrahepatic cholangiocarcinoma (NCCN.org).	detail...
NTRK2 fusion	breast cancer	sensitive	Larotrectinib	Guideline	Actionable	Vitrakvi (larotrectinib) therapy is included in guidelines for patients with recurrent unresectable or stage IV (M1) breast cancer harboring an NTRK fusion (NCCN.org).	detail...
KMT2A rearrange	acute myeloid leukemia	not applicable	N/A	Guideline	Prognostic	KMT2A rearrangements (t(v;11q23.3)) are associated with a poor/adverse prognosis in patients with non-APL acute myeloid leukemia (NCCN.org).	detail...
ALK rearrange	inflammatory myofibroblastic tumor	sensitive	Crizotinib	Guideline	Actionable	Xalkori (crizotinib) is included in guidelines as first-line therapy for patients with advanced, recurrent, metastatic, or inoperable inflammatory myofibroblastic tumor harboring ALK translocations (NCCN.org).	detail...
MLH1 negative	endometrial carcinoma	sensitive	Avelumab	Guideline	Actionable	Bavencio (avelumab) is included in guidelines as a second-line or subsequent-line therapy for patients with high microsatellite instability (MSI-H) or mismatch repair deficient (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) recurrent endometrial carcinoma (NCCN.org).	detail...
MSH6 negative	ovary epithelial cancer	sensitive	Dostarlimab-gxly	Guideline	Actionable	Jemperli (dostarlimab-gxly) is included in guidelines as systemic therapy for patients with recurrent or advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
FGFR1 fusion	salivary gland cancer	sensitive	Erdafitinib	Guideline	Actionable	Balversa (erdafitinib) is included in guidelines for patients with unresectable locally advanced, recurrent, or metastatic salivary gland tumors harboring FGFR mutations or fusions (category 2B) who received prior systemic therapy and have no alternative systemic therapy available (NCCN.org).	detail...
BRAF wild-type	rectum cancer	predicted - sensitive	Cetuximab	Guideline	Actionable	Erbitux (cetuximab), alone and in combination with chemotherapy, is included in guidelines for patients with advanced or metastatic rectal cancer that is BRAF wild-type, KRAS wild-type, and NRAS wild-type (NCCN.org).	detail...
NTRK1 fusion	esophagus squamous cell carcinoma	sensitive	Repotrectinib	Guideline	Actionable	Augtyro (repotrectinib) is included in guidelines as second-line or subsequent therapy for patients with unresectable locally advanced, recurrent, or metastatic esophageal squamous cell carcinoma with an NTRK fusion (NCCN.org).	detail...
FGFR2 act mut	oral cavity cancer	sensitive	Erdafitinib	Guideline	Actionable	Balversa (erdafitinib) is included in guidelines as subsequent-line therapy (category 2B) for patients with oral cavity cancer harboring FGFR mutations or fusions and with no alternative options (NCCN.org).	detail...
TP53 mutant	mantle cell lymphoma	sensitive	Acalabrutinib + Cyclophosphamide + Cytarabine + Dexamethasone + Doxorubicin + Prednisone + Rituximab + Vincristine Sulfate	Guideline	Actionable	The combination of Calquence (acalabrutinib) plus RCHOP alternating with Rituxan (rituximab), Adexone (dexamethasone), Cytosar-U (cytarabine) plus a platinum is included in guidelines as induction therapy for patients with mantle cell lymphoma harboring a TP53 mutation (NCCN.org).	detail...
RET fusion	oncocytic carcinoma of the thyroid	sensitive	Selpercatinib	Guideline	Actionable	Retevmo (selpercatinib) is included in guidelines for patients with RAI-refractory oncocytic thyroid carcinoma harboring a RET fusion with progressive or symptomatic disease (NCCN.org).	detail...
NTRK1 fusion	cervical cancer	sensitive	Repotrectinib	Guideline	Actionable	Augtyro (repotrectinib) is included in guidelines as second-line or subsequent therapy (category 2A) for patients with recurrent or metastatic cervical cancer harboring an NTRK fusion (NCCN.org).	detail...
MLH1 negative	gallbladder cancer	sensitive	Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab) is included in guidelines as primary therapy and subsequent-line therapy for patients with unresectable or metastatic biliary tract cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC), including gallbladder cancer (NCCN.org).	detail...
BRAF V600E	extrahepatic bile duct carcinoma	sensitive	Dabrafenib + Trametinib	Guideline	Actionable	Tafinlar (dabrafenib) in combination with Mekinist (trametinib) is included in guidelines as subsequent-line therapy for patients with biliary cancer harboring BRAF V600E, including extrahepatic cholangiocarcinoma (NCCN.org).	detail...
MSH6 negative	appendix adenocarcinoma	sensitive	Cemiplimab	Guideline	Actionable	Libtayo (cemiplimab) is included in guidelines (category 2A) for patients with advanced or metastatic appendiceal adenocarcinoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
MSH6 negative	gastroesophageal junction adenocarcinoma	sensitive	Capecitabine + Nivolumab + Oxaliplatin	Guideline	Actionable	Opdivo (nivolumab), in combination with Xeloda (capecitabine) and Eloxatin (oxaliplatin) is included in guidelines as first-line therapy for patients with unresectable locally advanced, recurrent, or metastatic gastroesophageal junction adenocarcinoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
ATM mutant	breast cancer	not applicable	N/A	Guideline	Risk Factor	Germline ATM mutations are associated with increased risk of developing breast cancer (NCCN.org).	detail...
FLT3 exon14	acute myeloid leukemia	sensitive	Midostaurin	Guideline	Actionable	Rydapt (midostaurin) is included in guidelines as maintenance therapy for patients with acute myeloid leukemia harboring a mutation in the FLT3 tyrosine kinase domain (exons 14-23) (NCCN.org).	detail...
MLH1 negative	ovary epithelial cancer	sensitive	Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab) is included in guidelines as systemic therapy for patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
NTRK1 fusion	gastrointestinal stromal tumor	sensitive	Repotrectinib	Guideline	Actionable	Augtyro (repotrectinib) is included in guidelines as neoadjuvant therapy (category 2B) for patients with resectable disease and as first-line or second-line systemic therapy (category 2A) for patients with unresectable or metastatic gastrointestinal stromal tumor (GIST) harboring NTRK fusions (NCCN.org).	detail...
NTRK2 fusion	papillary thyroid carcinoma	sensitive	Entrectinib	Guideline	Actionable	Rozlytrek (entrectinib) is included in guidelines for patients with RAI-refractory papillary thyroid carcinoma harboring an NTRK fusion with progressive or symptomatic disease (NCCN.org).	detail...
MSH6 negative	hepatocellular carcinoma	sensitive	Dostarlimab-gxly	Guideline	Actionable	Jemperli (dostarlimab-gxly) is included in guidelines as subsequent therapy for patients with mismatch repair deficient (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) hepatocellular carcinoma (NCCN.org).	detail...
MSH6 negative	ampulla of Vater adenocarcinoma	sensitive	Ipilimumab + Nivolumab	Guideline	Actionable	Opdivo (nivolumab) and Yervoy (ipilimumab) combination therapy is included in guidelines as first-line or subsequent therapy for metastatic ampullary adenocarcinoma patients with deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
VHL inact mut	islet cell tumor	not applicable	N/A	Guideline	Risk Factor	Germline inactivating mutations in VHL result in von Hippel-Lindau (VHL) syndrome, which is associated with increased risk of developing pancreatic neuroendocrine tumors (NCCN.org).	detail...
NTRK1 fusion	anaplastic thyroid carcinoma	sensitive	Entrectinib	Guideline	Actionable	Rozlytrek (entrectinib) is included in guidelines as neoadjuvant treatment for anaplastic thyroid carcinoma patients harboring NTRK fusions with stage IVa or IVb borderline resectable disease, and as a preferred systemic therapy for those with metastatic disease (NCCN.org).	detail...
ALK rearrange	lung non-small cell carcinoma	no benefit	Nivolumab	Guideline	Actionable	Monotherapy with immune checkpoint inhibitors, including Opdivo (nivolumab), Keytruda (pembrolizumab), Tecentriq (atezolizumab), and Imfinzi (durvalumab), is not indicated for use as initial systemic therapy or subsequent therapy in non-small cell lung cancer patients harboring oncogenic drivers, including ALK rearrangement (NCCN.org).	detail...
IDH2 mutant	polycythemia vera	not applicable	N/A	Guideline	Prognostic	IDH2 mutations are associated with inferior overall survival and leukemia-free survival in patients with polycythemia vera (NCCN.org).	detail...
FGFR1 act mut	glioblastoma	sensitive	Erdafitinib	Guideline	Actionable	Balversa (erdafitinib) is included in guidelines (category 2B) for patients with recurrent or progressive glioblastoma harboring FGFR mutations or fusions with no alternative treatment options (NCCN.org).	detail...
TP53 loss	chronic lymphocytic leukemia/small lymphocytic lymphoma	sensitive	Alemtuzumab + Rituximab	Guideline	Actionable	Campath (alemtuzumab) combined with Rituxan (rituximab) is included in guidelines as therapy for patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma with TP53 loss after prior BTK inhibitor-based and BCL2 inhibitor-containing regimens (NCCN.org).	detail...
BRAF V600X	skin melanoma	sensitive	Dabrafenib + Pembrolizumab + Trametinib	Guideline	Actionable	Tafinlar (dabrafenib) plus Mekinist (trametinib) in combination with an immune checkpoint inhibitor, such as Keytruda (pembrolizumab), is included in guidelines as second-line or subsequent therapy (category 2A) for patients with metastatic or unresectable cutaneous melanoma harboring a BRAF V600 mutation (NCCN.org).	detail...
MSH6 mutant	endometrial carcinoma	not applicable	N/A	Guideline	Risk Factor	Germline mutations in MSH6 result in Lynch syndrome, which is associated with increased risk of developing endometrial carcinoma (NCCN.org).	detail...
MLH1 negative	small intestine adenocarcinoma	sensitive	Cosibelimab	Guideline	Actionable	Unloxcyt (cosibelimab) is included in guidelines as systemic therapy (category 2A) for patients with advanced or metastatic small bowel adenocarcinoma with deficient mismatch repair (dMMR, often defined by the loss of MLH1, MSH2, MSH6, or PMS2 expression by IHC) (NCCN.org).	detail...
MLH1 negative	rectum cancer	sensitive	Tislelizumab	Guideline	Actionable	Tevimbra (tislelizumab) is included in guidelines (category 2A) for patients with advanced or metastatic rectal cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
NTRK2 fusion	gastroesophageal junction adenocarcinoma	sensitive	Repotrectinib	Guideline	Actionable	Augtyro (repotrectinib) is included in guidelines as second-line or subsequent therapy for patients with unresectable locally advanced, recurrent, or metastatic gastroesophageal junction adenocarcinoma with an NTRK fusion (NCCN.org).	detail...
ROS1 rearrange ROS1 G2032R	lung non-small cell carcinoma	sensitive	Taletrectinib	Guideline	Actionable	Ibtrozi (taletrectinib) is included in guidelines as a subsequent therapy for patients with ROS1 rearranged non-small cell lung cancer harboring ROS1 G2032R (NCCN.org).	detail...
FGFR1 fusion	glioblastoma	sensitive	Erdafitinib	Guideline	Actionable	Balversa (erdafitinib) is included in guidelines (category 2B) for patients with recurrent or progressive glioblastoma harboring FGFR mutations or fusions with no alternative treatment options (NCCN.org).	detail...
NTRK2 fusion	neuroendocrine tumor	sensitive	Entrectinib	Guideline	Actionable	Rozlytrek (entrectinib) is included in guidelines for patients with unresectable or metastatic extrapulmonary poorly differentiated neuroendocrine carcinoma, large or small cell carcinoma, or mixed neuroendocrine/non-neuroendocrine neoplasms harboring an NTRK fusion who have progressed on or following prior treatment (NCCN.org).	detail...
NRAS exon4	colon cancer	resistant	Panitumumab	Guideline	Actionable	Vectibix (panitumumab) is not indicated for use in colon cancer patients with NRAS exon 4 mutations (NCCN.org).	detail...
TP53 loss TP53 mut	chronic lymphocytic leukemia/small lymphocytic lymphoma	not applicable	N/A	Guideline	Prognostic	The presence of a TP53 mutation combined with TP53 loss is associated with shorter progression-free survival and overall survival with chemoimmunotherapy, fixed duration venetoclax-based regimens, and covalent BTK inhibitors in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (NCCN.org).	detail...
RET fusion	colon cancer	sensitive	Selpercatinib	Guideline	Actionable	Retevmo (selpercatinib) is included in guidelines for patients with metastatic colon cancer harboring RET fusions (NCCN.org).	detail...
ROS1 rearrange ROS1 G2032R	lung non-small cell carcinoma	sensitive	Repotrectinib	Guideline	Actionable	Augtyro (repotrectinib) is included in guidelines as a subsequent therapy for patients with ROS1 rearranged non-small cell lung cancer harboring ROS1 G2032R (NCCN.org).	detail...
MLH1 negative	esophagus adenocarcinoma	sensitive	Fluorouracil + Nivolumab + Oxaliplatin	Guideline	Actionable	Opdivo (nivolumab), in combination with Adrucil (fluorouracil) and Eloxatin (oxaliplatin) is included in guidelines as first-line therapy for patients with unresectable locally advanced, recurrent, or metastatic esophageal adenocarcinoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
NTRK2 fusion	colon cancer	sensitive	Repotrectinib	Guideline	Actionable	Augtyro (repotrectinib) is included in guidelines as second-line or subsequent therapy (category 2A) for patients with advanced or metastatic colon cancer harboring an NTRK fusion (NCCN.org).	detail...
NRAS wild-type	rectum cancer	predicted - sensitive	Cetuximab	Guideline	Actionable	Erbitux (cetuximab), alone and in combination with chemotherapy, is included in guidelines for patients with advanced or metastatic rectal cancer that is BRAF wild-type, KRAS wild-type, and NRAS wild-type (NCCN.org).	detail...
MLH1 negative	intrahepatic cholangiocarcinoma	sensitive	Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab) is included in guidelines as primary therapy and subsequent-line therapy for patients with unresectable or metastatic biliary tract cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC), including intrahepatic cholangiocarcinoma (NCCN.org).	detail...
NTRK2 fusion	hepatocellular carcinoma	sensitive	Larotrectinib	Guideline	Actionable	Vitrakvi (larotrectinib) is included in guidelines as subsequent-line therapy for patients with hepatocellular carcinoma harboring an NTRK fusion (NCCN.org).	detail...
MSH6 negative	colon cancer	sensitive	Tislelizumab	Guideline	Actionable	Tevimbra (tislelizumab) is included in guidelines (category 2A) for patients with advanced or metastatic colon cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
MSH6 negative	esophagus squamous cell carcinoma	sensitive	Dostarlimab-gxly	Guideline	Actionable	Jemperli (dostarlimab-gxly) is included in guidelines as second-line or subsequent therapy for patients with unresectable locally advanced, recurrent, or metastatic esophageal squamous cell carcinoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
TP53 mutant	mantle cell lymphoma	sensitive	Acalabrutinib + Rituximab	Guideline	Actionable	The combination of Calquence (acalabrutinib) and Rituxan (rituximab) is included in guidelines as induction therapy for patients with mantle cell lymphoma harboring a TP53 mutation (NCCN.org).	detail...
BRAF V600E	colon cancer	sensitive	Cetuximab + Encorafenib + Fluorouracil + Irinotecan + Leucovorin	Guideline	Actionable	Braftovi (encorafenib) in combination with Erbitux (cetuximab) and FOLFIRI is included in guidelines as a preferred initial therapy (category 2A) for patients with advanced or metastatic colon cancer harboring BRAF V600E (NCCN.org).	detail...
MSH6 negative	maxillary sinus cancer	sensitive	Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab) is included in guidelines as first- and subsequent-line therapy for patients with mismatch repair deficient (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) recurrent, unresectable, or metastatic maxillary sinus cancer (NCCN.org).	detail...
MLH1 negative	small intestine adenocarcinoma	sensitive	Avelumab	Guideline	Actionable	Bavencio (avelumab) is included in guidelines as systemic therapy (category 2A) for patients with advanced or metastatic small bowel adenocarcinoma with deficient mismatch repair (dMMR, often defined by the loss of MLH1, MSH2, MSH6, or PMS2 expression by IHC) (NCCN.org).	detail...
NTRK1 fusion	Erdheim-Chester disease	sensitive	Larotrectinib	Guideline	Actionable	Vitrakvi (larotrectinib) is included in guidelines as first-line or subsequent-line therapy for patients with Erdheim-Chester disease harboring NTRK1 fusions (NCCN.org).	detail...
NTRK2 fusion	gallbladder cancer	sensitive	Entrectinib	Guideline	Actionable	Rozlytrek (entrectinib) is included in guidelines as primary and subsequent-line therapy for patients with unresectable or metastatic biliary tract cancer harboring an NTRK fusion, including gallbladder cancer (NCCN.org).	detail...
NTRK2 fusion	uterine corpus sarcoma	sensitive	Larotrectinib	Guideline	Actionable	Vitrakvi (larotrectinib) is included in guidelines as first-line therapy for patients with advanced, recurrent, metastatic, or inoperable uterine sarcoma harboring an NTRK fusion (NCCN.org).	detail...
NTRK2 fusion	appendix adenocarcinoma	sensitive	Entrectinib	Guideline	Actionable	Rozlytrek (entrectinib) is included in guidelines (category 2A) as second-line or subsequent therapy for patients with advanced or metastatic appendiceal adenocarcinoma harboring an NTRK fusion (NCCN.org).	detail...
FLT3 exon 14 ins	acute myeloid leukemia	sensitive	Cytarabine + Quizartinib	Guideline	Actionable	Vanflyta (quizartinib) in combination with Cytosar-U (cytarabine) is included in guidelines as consolidation therapy for patients with acute myeloid leukemia harboring a FLT3 internal tandem duplication (FLT3-ITD) mutation (NCCN.org).	detail...
NTRK1 fusion	hepatocellular carcinoma	sensitive	Larotrectinib	Guideline	Actionable	Vitrakvi (larotrectinib) is included in guidelines as subsequent-line therapy for patients with hepatocellular carcinoma harboring an NTRK fusion (NCCN.org).	detail...
MSH6 negative	chondrosarcoma	sensitive	Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab) is included in guidelines as systemic therapy for metastatic chondrosarcoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
NTRK2 fusion	follicular thyroid carcinoma	sensitive	Repotrectinib	Guideline	Actionable	Augtyro (repotrectinib) is included in guidelines for patients with RAI-refractory oncocytic thyroid carcinoma harboring an NTRK fusion with progressive or symptomatic disease (NCCN.org).	detail...
MSH6 negative	esophagus adenocarcinoma	sensitive	Fluorouracil + Nivolumab + Oxaliplatin	Guideline	Actionable	Opdivo (nivolumab), in combination with Adrucil (fluorouracil) and Eloxatin (oxaliplatin) is included in guidelines as first-line therapy for patients with unresectable locally advanced, recurrent, or metastatic esophageal adenocarcinoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
NTRK2 fusion	high grade glioma	sensitive	Repotrectinib	Guideline	Actionable	Augtyro (repotrectinib) is included in guidelines as adjuvant therapy for pediatric patients with diffuse high-grade gliomas harboring NTRK fusions, or as a preferred regimen for patients with recurrent or progressive disease (NCCN.org).	detail...
FGFR1 act mut	breast cancer	sensitive	Erdafitinib	Guideline	Actionable	Balversa (erdafitinib) is included in guidelines for patients with stage IV (M1) breast cancer harboring FGFR fusion or mutations (category 2B) (NCCN.org).	detail...
FGFR3 act mut	supraglottis cancer	sensitive	Erdafitinib	Guideline	Actionable	Balversa (erdafitinib) is included in guidelines as subsequent-line therapy (category 2B) for patients with supraglottic larynx cancer harboring FGFR mutations or fusions and with no alternative options (NCCN.org).	detail...
NTRK1 fusion	salivary gland cancer	sensitive	Repotrectinib	Guideline	Actionable	Augtyro (repotrectinib) is included in guidelines for patients with unresectable locally advanced, recurrent, or metastatic salivary gland tumors harboring an NTRK1 fusion (NCCN.org).	detail...
MSH6 negative	colon cancer	sensitive	Atezolizumab + Capecitabine + Oxaliplatin	Guideline	Actionable	Tecentriq (atezolizumab) in combination with Xeloda (capecitabine) and Eloxatin (oxaliplatin) is included in guidelines as adjuvant therapy for patients with colon cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
NTRK1 fusion	high grade glioma	sensitive	Entrectinib	Guideline	Actionable	Rozlytrek (entrectinib) is included in guidelines as adjuvant therapy for pediatric patients with diffuse high-grade gliomas harboring NTRK fusions, or as a preferred regimen for patients with recurrent or progressive disease (NCCN.org).	detail...
NTRK2 fusion	rectum cancer	sensitive	Larotrectinib	Guideline	Actionable	Vitrakvi (larotrectinib) is included in guidelines for advanced or metastatic rectal cancer patients with an NTRK fusion (NCCN.org).	detail...
TP53 mutant	chronic lymphocytic leukemia/small lymphocytic lymphoma	sensitive	Ibrutinib + Lisocabtagene maraleucel	Guideline	Actionable	Breyanzi (lisocabtagene maraleucel) in combination with Imbruvica (ibrutinib) is included in guidelines for patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma with a TP53 mutation after prior BTK inhibitor-based and BCL2 inhibitor-containing regimens (NCCN.org).	detail...
ATM mutant	pancreatic cancer	not applicable	N/A	Guideline	Risk Factor	Germline ATM mutations are associated with increased risk of developing pancreatic cancer (NCCN.org).	detail...
NTRK2 fusion	Squamous Cell Carcinoma of Unknown Primary	sensitive	Larotrectinib	Guideline	Actionable	Vitrakvi (larotrectinib) is included in guidelines for patients with squamous cell carcinoma of unknown primary harboring NTRK2 fusions (NCCN.org).	detail...
NRAS exon4	rectum cancer	resistant	Cetuximab	Guideline	Actionable	Erbitux (cetuximab) is not indicated for use in rectum cancer patients with NRAS exon 4 mutations (NCCN.org).	detail...
NTRK1 fusion	uterine corpus sarcoma	sensitive	Repotrectinib	Guideline	Actionable	Augtyro (repotrectinib) is included in guidelines as first-line therapy for patients with advanced, recurrent, metastatic, or inoperable uterine sarcoma harboring an NTRK fusion (NCCN.org).	detail...
MSH6 negative	rectum cancer	sensitive	Cosibelimab	Guideline	Actionable	Unloxcyt (cosibelimab) is included in guidelines (category 2A) for patients with advanced or metastatic rectal cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MSH6, MSH2, MLH1, or PMS2 expression by IHC) (NCCN.org).	detail...
MLH1 negative	small intestine adenocarcinoma	sensitive	Atezolizumab + Capecitabine + Oxaliplatin	Guideline	Actionable	Tecentriq (atezolizumab) in combination with Xeloda (capecitabine) and Eloxatin (oxaliplatin) is included in guidelines as adjuvant therapy (category 2A) for patients with small bowel adenocarcinoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, MSH2, MSH6, or PMS2 expression by IHC) (NCCN.org).	detail...
FLT3 exon16	acute myeloid leukemia	sensitive	Cytarabine + Idarubicin + Midostaurin	Guideline	Actionable	Rydapt (midostaurin) in combination with Idamycin (idarubicin) and Cytosar-U (cytarabine) is included in guidelines for patients with acute myeloid leukemia harboring a mutation in the FLT3 tyrosine kinase domain (exons 14-23) (NCCN.org).	detail...
RET L790X	medullary thyroid carcinoma	not applicable	N/A	Guideline	Risk Factor	Germline RET L790X mutations result in multiple endocrine neoplasia, type 2A (MEN 2A), which is associated with increased risk of developing thyroid medullary carcinoma (NCCN.org).	detail...
FLT3 exon21	acute myeloid leukemia	sensitive	Gilteritinib	Guideline	Actionable	Xospata (gilteritinib) is included in guidelines for patients with relapsed or refractory acute myeloid leukemia harboring a mutation in the FLT3 tyrosine kinase domain (exons 14-23) (NCCN.org).	detail...
NTRK2 fusion	vulva adenocarcinoma	sensitive	Entrectinib	Guideline	Actionable	Rozlytrek (entrectinib) is included in guidelines as a second-line or subsequent therapy for patients with advanced or recurrent/metastatic vulvar adenocarcinoma harboring an NTRK fusion (NCCN.org).	detail...
MLH1 negative	stomach cancer	sensitive	Ipilimumab + Nivolumab	Guideline	Actionable	Opdivo (nivolumab), in combination with Yervoy (ipilimumab), is included in guidelines as first-line, second-line, or subsequent therapy for patients with unresectable locally advanced, recurrent, or metastatic gastric cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
FGFR2 fusion	glioblastoma	sensitive	Erdafitinib	Guideline	Actionable	Balversa (erdafitinib) is included in guidelines (category 2B) for patients with recurrent or progressive glioblastoma harboring FGFR mutations or fusions with no alternative treatment options (NCCN.org).	detail...
KMT2A rearrange	B-cell acute lymphoblastic leukemia	not applicable	N/A	Guideline	Diagnostic	KMT2A rearrangements (t(v;11q23.3)) aid in the diagnosis of B-cell acute lymphoblastic leukemia (NCCN.org).	detail...
BRAF V600E	anaplastic astrocytoma	sensitive	Cobimetinib + Vemurafenib	Guideline	Actionable	Combination of Zelboraf (vemurafenib) and Cotellic (cobimetinib) is included in guidelines for patients with recurrent anaplastic gliomas harboring BRAF V600E, including anaplastic astrocytoma (NCCN.org).	detail...
MLH1 negative	esophagus squamous cell carcinoma	sensitive	Dostarlimab-gxly	Guideline	Actionable	Jemperli (dostarlimab-gxly) is included in guidelines as first-line, second-line, or subsequent therapy for patients with unresectable locally advanced, recurrent, or metastatic esophageal squamous cell carcinoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
MSH6 negative	rectum cancer	sensitive	Cemiplimab	Guideline	Actionable	Libtayo (cemiplimab) is included in guidelines (category 2A) for patients with advanced or metastatic rectal cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
MSH6 negative	small intestine adenocarcinoma	sensitive	Retifanlimab	Guideline	Actionable	Zynyz (retifanlimab) is included in guidelines as systemic therapy (category 2A) for patients with advanced or metastatic small bowel adenocarcinoma with deficient mismatch repair (dMMR, often defined by the loss of MSH6, MSH2, PMS2, or MLH1 expression by IHC) (NCCN.org).	detail...
MSH6 negative	ethmoid sinus cancer	sensitive	Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab) is included in guidelines as first- and subsequent-line therapy for patients with mismatch repair deficient (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) recurrent, unresectable, or metastatic ethmoid sinus cancer (NCCN.org).	detail...
MSH6 negative	esophagus squamous cell carcinoma	sensitive	Capecitabine + Nivolumab + Oxaliplatin	Guideline	Actionable	Opdivo (nivolumab), in combination with Xeloda (capecitabine) and Eloxatin (oxaliplatin) is included in guidelines as first-line therapy for patients with unresectable locally advanced, recurrent, or metastatic esophagus squamous cell carcinoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
ABL1 rearrange	myeloid neoplasm	sensitive	Asciminib	Guideline	Actionable	Scemblix (asciminib) is included in guidelines for patients with a myeloid/lymphoid neoplasm with eosinophilia harboring an ABL1 rearrangement (NCCN.org).	detail...
FGFR3 fusion	supraglottis cancer	sensitive	Erdafitinib	Guideline	Actionable	Balversa (erdafitinib) is included in guidelines as subsequent-line therapy (category 2B) for patients with supraglottic larynx cancer harboring FGFR mutations or fusions and with no alternative options (NCCN.org).	detail...
APC mutant	adrenocortical carcinoma	not applicable	N/A	Guideline	Risk Factor	Familial adenomatous polyposis results from germline mutations in the APC gene, and is associated with increased risk of developing adrenocortical carcinoma (NCCN.org).	detail...
BRAF V600E	pilocytic astrocytoma	sensitive	Cobimetinib + Vemurafenib	Guideline	Actionable	Zelboraf (vemurafenib) and Cotellic (cobimetinib) combination therapy is included in guidelines as an adjuvant treatment for patients with pilocytic astrocytoma harboring BRAF V600E (NCCN.org).	detail...
TP53 mutant	chronic lymphocytic leukemia/small lymphocytic lymphoma	sensitive	Ibrutinib	Guideline	Actionable	Imbruvica (ibrutinib) is included in guidelines as first-line therapy (category 2A) and second-line or subsequent therapy (category 1) for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with a TP53 mutation (NCCN.org).	detail...
MLH1 negative	appendix adenocarcinoma	sensitive	Nivolumab	Guideline	Actionable	Opdivo (nivolumab) is included in guidelines (category 2A) for patients with advanced or metastatic appendiceal adenocarcinoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
NRAS exon4	rectum cancer	resistant	Panitumumab	Guideline	Actionable	Vectibix (panitumumab) is not indicated for use in rectum cancer patients with NRAS exon 4 mutations (NCCN.org).	detail...
FLT3 exon14	acute myeloid leukemia	sensitive	Cytarabine + Midostaurin	Guideline	Actionable	Rydapt (midostaurin) in combination with Cytosar-U (cytarabine) is included in guidelines as consolidation therapy for patients with acute myeloid leukemia harboring a mutation in the FLT3 tyrosine kinase domain (exons 14-23) (NCCN.org).	detail...
FGFR3 act mut	breast cancer	sensitive	Erdafitinib	Guideline	Actionable	Balversa (erdafitinib) is included in guidelines for patients with stage IV (M1) breast cancer harboring FGFR fusion or mutations (category 2B) (NCCN.org).	detail...
NTRK1 fusion	soft tissue sarcoma	sensitive	Repotrectinib	Guideline	Actionable	Augtyro (repotrectinib) is included in guidelines as a preferred first-line or subsequent therapy for patients with soft tissue sarcoma harboring an NTRK1 fusion (NCCN.org).	detail...
IDH2 mutant	high grade glioma	not applicable	N/A	Guideline	Prognostic	IDH2 mutations are associated with a favorable prognosis in patients with glioma, and are associated with a survival benefit for patients treated with radiation or alkylator therapy (NCCN.org).	detail...
NTRK1 fusion	gastroesophageal junction adenocarcinoma	sensitive	Larotrectinib	Guideline	Actionable	Vitrakvi (larotrectinib) is included in guidelines as second-line or subsequent therapy for patients with unresectable locally advanced, recurrent, or metastatic gastroesophageal junction adenocarcinoma with an NTRK fusion (NCCN.org).	detail...
FGFR1 fusion	hypopharynx cancer	sensitive	Erdafitinib	Guideline	Actionable	Balversa (erdafitinib) is included in guidelines as subsequent-line therapy (category 2B) for patients with hypopharynx cancer harboring FGFR mutations or fusions and with no alternative options (NCCN.org).	detail...
DNMT3A mutant	myelofibrosis	not applicable	N/A	Guideline	Prognostic	DNMT3A mutations are associated with inferior overall survival in patients with primary myelofibrosis (NCCN.org).	detail...
NTRK1 fusion	small intestine adenocarcinoma	sensitive	Entrectinib	Guideline	Actionable	Rozlytrek (entrectinib) is included in guidelines for patients with metastatic small bowel adenocarcinoma with an NTRK fusion (NCCN.org).	detail...
MLH1 negative	esophagus squamous cell carcinoma	sensitive	Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab) is included in guidelines as first-line, second-line, or subsequent therapy for patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) esophageal squamous cell carcinoma that are unresectable, locally advanced, recurrent, or metastatic (NCCN.org).	detail...
PIK3CA act mut	colon cancer	sensitive	Aspirin	Guideline	Actionable	Aspirin is included in guidelines as adjuvant therapy (category 2A) for patients with advanced colon cancer harboring PIK3CA mutations, including hotspot mutations in exon 10 (reported as exon 9) and exon 21 (reported as exon 20), and other somatic mutations affecting the PI3K pathway genes PIK3R1 or PTEN (NCCN.org).	detail...
NTRK1 fusion	vaginal carcinoma	sensitive	Larotrectinib	Guideline	Actionable	Vitrakvi (larotrectinib) is included in guidelines as second-line or subsequent therapy for patients with recurrent or metastatic vaginal squamous cell carcinoma or adenocarcinoma harboring an NTRK fusion (NCCN.org).	detail...
BRAF V600E	ovary epithelial cancer	sensitive	Dabrafenib + Trametinib	Guideline	Actionable	Tafinlar (dabrafenib) and Mekinist (trametinib) combination therapy is included in guidelines as systemic therapy for patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer harboring BRAF V600E (NCCN.org).	detail...
NTRK2 fusion	esophagus squamous cell carcinoma	sensitive	Repotrectinib	Guideline	Actionable	Augtyro (repotrectinib) is included in guidelines as second-line or subsequent therapy for patients with unresectable locally advanced, recurrent, or metastatic esophageal squamous cell carcinoma with an NTRK fusion (NCCN.org).	detail...
FLT3 exon15	acute myeloid leukemia	sensitive	Cytarabine + Daunorubicin + Midostaurin	Guideline	Actionable	Rydapt (midostaurin), in combination with Cerubidine (daunorubicin) and Cytosar-U (cytarabine), is included in guidelines for patients with acute myeloid leukemia harboring a mutation in the FLT3 tyrosine kinase domain (exons 14-23) (NCCN.org).	detail...
NRAS mutant	Erdheim-Chester disease	sensitive	Cobimetinib	Guideline	Actionable	Cotellic (cobimetinib) is included in guidelines as preferred first-line or subsequent-line therapy for patients with Erdheim-Chester disease harboring mutations in the MAPK pathway such as ARAF, NRAS, KRAS, MAP2K1/2, PIK3CA, or with no detectable mutations, or for whom testing is not available (NCCN.org).	detail...
BRAF V600E	rectum cancer	sensitive	Encorafenib + Fluorouracil + Leucovorin + Oxaliplatin + Panitumumab	Guideline	Actionable	Braftovi (encorafenib) in combination with Vectibix (panitumumab) and FOLFOX is included in guidelines as a preferred initial therapy (category 2A) for patients with advanced or metastatic rectal cancer harboring BRAF V600E (NCCN.org).	detail...
MLH1 negative	rectum cancer	sensitive	Cemiplimab	Guideline	Actionable	Libtayo (cemiplimab) is included in guidelines (category 2A) for patients with advanced or metastatic rectal cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
NTRK1 fusion	anaplastic astrocytoma	sensitive	Entrectinib	Guideline	Actionable	Rozlytrek (entrectinib) is included in guidelines for patients with recurrent anaplastic gliomas harboring an NTRK fusion, including anaplastic astrocytoma (NCCN.org).	detail...
NTRK1 fusion	vulva adenocarcinoma	sensitive	Repotrectinib	Guideline	Actionable	Augtyro (repotrectinib) is included in guidelines as a second-line or subsequent therapy for patients with advanced or recurrent/metastatic vulvar adenocarcinoma harboring an NTRK fusion (NCCN.org).	detail...
TP53 mutant	chronic lymphocytic leukemia/small lymphocytic lymphoma	sensitive	Lisocabtagene maraleucel	Guideline	Actionable	Breyanzi (lisocabtagene maraleucel) is included in guidelines for patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma with a TP53 mutation after prior BTK inhibitor-based and BCL2 inhibitor-containing regimens (NCCN.org).	detail...
NTRK1 fusion	anaplastic thyroid carcinoma	sensitive	Larotrectinib	Guideline	Actionable	Vitrakvi (larotrectinib) is included in guidelines as neoadjuvant treatment for anaplastic thyroid carcinoma patients harboring NTRK fusions with stage IVa or IVb borderline resectable disease, and as a preferred systemic therapy for those with metastatic disease (NCCN.org).	detail...
TP53 loss	chronic lymphocytic leukemia/small lymphocytic lymphoma	sensitive	Rituximab + Venetoclax	Guideline	Actionable	Venclexta (venetoclax) combined with Rituxan (rituximab) is included in guidelines as second-line or subsequent therapy for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with TP53 loss (NCCN.org).	detail...
FLT3 exon15	acute myeloid leukemia	sensitive	Cytarabine + Midostaurin	Guideline	Actionable	Rydapt (midostaurin) in combination with Cytosar-U (cytarabine) is included in guidelines as consolidation therapy for patients with acute myeloid leukemia harboring a mutation in the FLT3 tyrosine kinase domain (exons 14-23) (NCCN.org).	detail...
MSH6 negative	stomach cancer	sensitive	Capecitabine + Nivolumab + Oxaliplatin	Guideline	Actionable	Opdivo (nivolumab), in combination with Xeloda (capecitabine) and Eloxatin (oxaliplatin) is included in guidelines as first-line therapy for patients with unresectable locally advanced, recurrent, or metastatic gastric cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
FGFR3 fusion	lung non-small cell carcinoma	sensitive	Erdafitinib	Guideline	Actionable	Balversa (erdafitinib) is included in guidelines for patients with metastatic non-small cell lung cancer harboring oncogenic or likely oncogenic FGFR alterations (NCCN.org).	detail...
IDH1 act mut	chondrosarcoma	sensitive	Ivosidenib	Guideline	Actionable	Tibsovo (ivosidenib) is included in guidelines as systemic therapy for patients with conventional or dedifferentiated chondrosarcoma harboring an IDH1 activating mutation (NCCN.org).	detail...
MSH6 negative	salivary gland cancer	sensitive	Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab) is included in guidelines for patients with recurrent, unresectable, or metastatic salivary gland tumors with deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
FLT3 exon22	acute myeloid leukemia	sensitive	Cytarabine + Daunorubicin + Midostaurin	Guideline	Actionable	Rydapt (midostaurin), in combination with Cerubidine (daunorubicin) and Cytosar-U (cytarabine), is included in guidelines for patients with acute myeloid leukemia harboring a mutation in the FLT3 tyrosine kinase domain (exons 14-23) (NCCN.org).	detail...
ATM mutant	prostate cancer	not applicable	N/A	Guideline	Risk Factor	Germline ATM mutations are associated with increased risk of developing prostate cancer (NCCN.org).	detail...
NTRK1 fusion	stomach cancer	sensitive	Repotrectinib	Guideline	Actionable	Augtyro (repotrectinib) is included in guidelines as second-line or subsequent therapy for patients with unresectable locally advanced, recurrent, or metastatic gastric cancer harboring an NTRK1 fusion (NCCN.org).	detail...
BRAF V600E	follicular thyroid carcinoma	sensitive	Dabrafenib + Trametinib	Guideline	Actionable	The combination of Tafinlar (dabrafenib) and Mekinist (trametinib) is included in guidelines for patients with RAI-refractory follicular thyroid carcinoma harboring BRAF V600E who have progressed on therapy and have no further treatment options (NCCN.org).	detail...
MSH6 mutant	rectum cancer	not applicable	N/A	Guideline	Risk Factor	Lynch syndrome results from germline mutations in DNA mismatch repair genes including MLH1, MSH2, MSH6, and PMS2, and is associated with increased risk of developing colorectal cancer (NCCN.org).	detail...
FGFR2 fusion	intrahepatic cholangiocarcinoma	sensitive	Futibatinib	Guideline	Actionable	Lytgobi (futibatinib) is included in guidelines as subsequent-line therapy (category 2A) for patients with cholangiocarcinoma harboring an FGFR2 fusion or rearrangement (NCCN.org).	detail...
PIK3CA mutant	Erdheim-Chester disease	sensitive	Everolimus	Guideline	Actionable	Afinitor (everolimus) is included in guidelines as first-line or subsequent-line therapy for patients with Erdheim-Chester disease harboring PIK3CA mutations (NCCN.org).	detail...
JAK1 mutant	childhood B-cell acute lymphoblastic leukemia	not applicable	N/A	Guideline	Prognostic	JAK1 mutations are associated with a poor prognosis in pediatric patients with B-cell acute lymphoblastic leukemia (NCCN.org).	detail...
NTRK1 fusion	anaplastic oligodendroglioma	sensitive	Entrectinib	Guideline	Actionable	Rozlytrek (entrectinib) is included in guidelines for patients with recurrent anaplastic gliomas harboring an NTRK fusion, including anaplastic oligodendroglioma (NCCN.org).	detail...
FGFR1 act mut	salivary gland cancer	sensitive	Erdafitinib	Guideline	Actionable	Balversa (erdafitinib) is included in guidelines for patients with unresectable locally advanced, recurrent, or metastatic salivary gland tumors harboring FGFR mutations or fusions (category 2B) who received prior systemic therapy and have no alternative systemic therapy available (NCCN.org).	detail...
MSH6 negative	stomach cancer	sensitive	Capecitabine + Oxaliplatin + Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab), in combination with Xeloda (capecitabine) and Eloxatin (oxaliplatin) is included in guidelines as first-line therapy for patients with unresectable locally advanced, recurrent, or metastatic gastric cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
IDH1 act mut	astrocytoma, IDH-mutant, grade 2	sensitive	Vorasidenib	Guideline	Actionable	Voranigo (vorasidenib) is included in guidelines for patients with WHO grade 2 astrocytoma harboring an IDH1 activating mutation with no residual/measurable disease or as adjuvant therapy after surgery/biopsy (category 1) and for patients with recurrent or progressive disease (category 2A) (NCCN.org).	detail...
BRAF V600E	follicular thyroid carcinoma	sensitive	Dabrafenib	Guideline	Actionable	Tafinlar (dabrafenib) is included in guidelines for patients with RAI-refractory follicular thyroid carcinoma harboring BRAF V600E for whom clinical trials or other systemic therapies are not available or appropriate (category 2B) (NCCN.org).	detail...
NTRK1 fusion	pleomorphic xanthoastrocytoma	sensitive	Repotrectinib	Guideline	Actionable	Augtyro (repotrectinib) is included in guidelines (category 2B) for patients with recurrent or progressive circumscribed glioma, including pleomorphic xanthoastrocytoma, harboring an NTRK fusion (NCCN.org).	detail...
TP53 loss	chronic lymphocytic leukemia/small lymphocytic lymphoma	sensitive	Venetoclax + Zanubrutinib	Guideline	Actionable	Venclexta (venetoclax) combined with Brukinsa (zanubrutinib) is included in guidelines as first-line therapy for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with TP53 loss (NCCN.org).	detail...
MSH6 negative	rectum cancer	sensitive	Dostarlimab-gxly	Guideline	Actionable	Jemperli (dostarlimab-gxly) is included in guidelines as subsequent therapy for patients with advanced or metastatic rectal cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
TP53 mutant	chronic lymphocytic leukemia/small lymphocytic lymphoma	sensitive	Methylprednisolone + Obinutuzumab	Guideline	Actionable	Artisone-Wyeth (methylprednisolone) combined with Gazyva (obinutuzumab) is included in guidelines as first-line therapy for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with a TP53 mutation and for patients with relapsed or refractory disease after prior BTK inhibitor and BLC2 inhibitor-based regimens (NCCN.org).	detail...
NTRK1 fusion	low grade glioma	sensitive	Entrectinib	Guideline	Actionable	Rozlytrek (entrectinib) is included in guidelines for patients with recurrent or progressive low grade glioma harboring an NTRK fusion (NCCN.org).	detail...
FLT3 exon20	acute myeloid leukemia	sensitive	Cytarabine + Idarubicin + Midostaurin	Guideline	Actionable	Rydapt (midostaurin) in combination with Idamycin (idarubicin) and Cytosar-U (cytarabine) is included in guidelines for patients with acute myeloid leukemia harboring a mutation in the FLT3 tyrosine kinase domain (exons 14-23) (NCCN.org).	detail...
BRAF V600X	skin melanoma	sensitive	Dabrafenib + Trametinib	Guideline	Actionable	Tafinlar (dabrafenib) and Mekinist (trametinib) combination therapy is included in guidelines as neoadjuvant or adjuvant therapy for stage III disease and as second-line or subsequent therapy for patients with metastatic or unresectable cutaneous melanoma harboring a BRAF V600 mutation (NCCN.org).	detail...
FGFR3 fusion	ethmoid sinus cancer	sensitive	Erdafitinib	Guideline	Actionable	Balversa (erdafitinib) is included in guidelines as subsequent-line therapy (category 2B) for patients with ethmoid sinus cancer harboring FGFR mutations or fusions and with no alternative options (NCCN.org).	detail...
VHL inact mut	pheochromocytoma	not applicable	N/A	Guideline	Risk Factor	Germline inactivating mutations in VHL result in von Hippel-Lindau (VHL) syndrome, which is associated with increased risk of developing pheochromocytoma (NCCN.org).	detail...
IDH2 mutant	acute myeloid leukemia	sensitive	Enasidenib	Guideline	Actionable	Idhifa (enasidenib) is included in guidelines for patients with relapsed or refractory acute myeloid leukemia harboring an IDH2 mutation (NCCN.org).	detail...
MLH1 negative	chordoma	sensitive	Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab) is included in guidelines as systemic therapy for metastatic chordoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
PIK3CA mutant	Erdheim-Chester disease	sensitive	Cobimetinib	Guideline	Actionable	Cotellic (cobimetinib) is included in guidelines as preferred first-line or subsequent-line therapy for patients with Erdheim-Chester disease harboring mutations in the MAPK pathway such as ARAF, NRAS, KRAS, MAP2K1/2, PIK3CA, or with no detectable mutations, or for whom testing is not available (NCCN.org).	detail...
NTRK1 fusion	small intestine adenocarcinoma	sensitive	Larotrectinib	Guideline	Actionable	Vitrakvi (larotrectinib) is included in guidelines for patients with metastatic small bowel adenocarcinoma with an NTRK fusion (NCCN.org).	detail...
FGFR1 act mut	glottis cancer	sensitive	Erdafitinib	Guideline	Actionable	Balversa (erdafitinib) is included in guidelines as subsequent-line therapy (category 2B) for patients with glottic larynx cancer harboring FGFR mutations or fusions and with no alternative options (NCCN.org).	detail...
BRAF fusion	pilocytic astrocytoma	sensitive	Selumetinib	Guideline	Actionable	Koselugo (selumetinib) is included in guidelines for patients with recurrent or progressive pilocytic astrocytoma harboring a BRAF fusion (NCCN.org).	detail...
NTRK1 fusion	gastroesophageal junction adenocarcinoma	sensitive	Repotrectinib	Guideline	Actionable	Augtyro (repotrectinib) is included in guidelines as second-line or subsequent therapy for patients with unresectable locally advanced, recurrent, or metastatic gastroesophageal junction adenocarcinoma with an NTRK fusion (NCCN.org).	detail...
MSH6 negative	vulva adenocarcinoma	sensitive	Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab) is included in guidelines as a second-line or subsequent therapy for patients with advanced or recurrent/metastatic MSI high or dMMR (often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) vulva adenocarcinoma (NCCN.org).	detail...
ATM mutant	ovarian cancer	not applicable	N/A	Guideline	Risk Factor	Germline ATM mutations are associated with increased risk of developing ovarian cancer (NCCN.org).	detail...
MLH1 negative	colon cancer	sensitive	Cosibelimab	Guideline	Actionable	Unloxcyt (cosibelimab) is included in guidelines (category 2A) for patients with advanced or metastatic colon cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, MSH2, MSH6, or PMS2 expression by IHC) (NCCN.org).	detail...
BRAF V600E	colon cancer	sensitive	Capecitabine + Cetuximab + Encorafenib + Oxaliplatin	Guideline	Actionable	Braftovi (encorafenib) in combination with Erbitux (cetuximab) and CAPEOX is included in guidelines as an initial therapy (category 2A) for patients with advanced or metastatic colon cancer harboring BRAF V600E (NCCN.org).	detail...
MSH6 negative	soft tissue sarcoma	sensitive	Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab) is included in guidelines as systemic therapy for soft tissue sarcoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC), regardless of sarcoma sub-type (NCCN.org).	detail...
FGFR2 act mut	glioblastoma	sensitive	Erdafitinib	Guideline	Actionable	Balversa (erdafitinib) is included in guidelines (category 2B) for patients with recurrent or progressive glioblastoma harboring FGFR mutations or fusions with no alternative treatment options (NCCN.org).	detail...
MLH1 negative	hepatocellular carcinoma	sensitive	Dostarlimab-gxly	Guideline	Actionable	Jemperli (dostarlimab-gxly) is included in guidelines as subsequent therapy for patients with mismatch repair deficient (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) hepatocellular carcinoma (NCCN.org).	detail...
FGFR2 fusion	extrahepatic bile duct carcinoma	sensitive	Futibatinib	Guideline	Actionable	Lytgobi (futibatinib) is included in guidelines as subsequent-line therapy (category 2A) for patients with cholangiocarcinoma harboring an FGFR2 fusion or rearrangement (NCCN.org).	detail...
FGFR3 fusion	glioblastoma	sensitive	Erdafitinib	Guideline	Actionable	Balversa (erdafitinib) is included in guidelines (category 2B) for patients with recurrent or progressive glioblastoma harboring FGFR mutations or fusions with no alternative treatment options (NCCN.org).	detail...
FLT3 exon19	acute myeloid leukemia	sensitive	Midostaurin	Guideline	Actionable	Rydapt (midostaurin) is included in guidelines as maintenance therapy for patients with acute myeloid leukemia harboring a mutation in the FLT3 tyrosine kinase domain (exons 14-23) (NCCN.org).	detail...
MSH6 negative	esophagus adenocarcinoma	sensitive	Capecitabine + Oxaliplatin + Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab), in combination with Xeloda (capecitabine) and Eloxatin (oxaliplatin) is included in guidelines as first-line therapy for patients with unresectable locally advanced, recurrent, or metastatic esophageal adenocarcinoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
BRAF V600E	skin melanoma	sensitive	Binimetinib + Encorafenib	Guideline	Actionable	Braftovi (encorafenib) in combination with Mektovi (binimetinib) is included in guidelines as first-line and second-line therapy for patients with metastatic or unresectable cutaneous melanoma harboring BRAF V600E or V600K mutations (PMID: 30959471; NCCN.org).	detail... 30959471
FGFR2 fusion	hypopharynx cancer	sensitive	Erdafitinib	Guideline	Actionable	Balversa (erdafitinib) is included in guidelines as subsequent-line therapy (category 2B) for patients with hypopharynx cancer harboring FGFR mutations or fusions and with no alternative options (NCCN.org).	detail...
PTEN del	rectum cancer	sensitive	Aspirin	Guideline	Actionable	Aspirin is included in guidelines as adjuvant therapy (category 2A) for patients with advanced rectal cancer harboring deep PTEN deletions and other somatic mutations affecting the PI3K pathway genes PIK3CA, PIK3R1, or PTEN (NCCN.org).	detail...
RET fusion	anaplastic thyroid carcinoma	sensitive	Pralsetinib	Guideline	Actionable	Gavreto (pralsetinib) is included in guidelines as neoadjuvant treatment for anaplastic thyroid carcinoma patients harboring RET fusions with stage IVa or IVb borderline resectable disease, and as a preferred systemic therapy for those with metastatic disease (NCCN.org).	detail...
TP53 mutant	acute myeloid leukemia	sensitive	Decitabine	Guideline	Actionable	Dacogen (decitabine) is included in guidelines for adult patients with acute myeloid leukemia harboring a TP53 mutation (NCCN.org).	detail...
RET fusion	pheochromocytoma	sensitive	Selpercatinib	Guideline	Actionable	Retevmo (selpercatinib) is included in guidelines for patients with RET fusion-positive, locally unresectable or metastatic pheochromocytoma (NCCN.org).	detail...
BTK C481S	chronic lymphocytic leukemia/small lymphocytic lymphoma	resistant	Acalabrutinib	Guideline	Actionable	Calquence (acalabrutinib) is not indicated for use in patients with Imbruvica (ibrutinib)-refractory chronic lymphocytic leukemia/small lymphocytic lymphoma harboring BTK C481S (NCCN.org).	detail...
NTRK2 fusion	soft tissue sarcoma	sensitive	Larotrectinib	Guideline	Actionable	Vitrakvi (larotrectinib) is in guidelines for patients with soft tissue sarcoma harboring an NTRK fusion (NCCN.org).	detail...
FGFR3 act mut	transitional cell carcinoma	sensitive	Erdafitinib	Guideline	Actionable	Balversa (erdafitinib) is included in guidelines (category 1 for patients who have already received platinum and a checkpoint inhibitor) as second-line or subsequent-line therapy for patients with advanced or metastatic urothelial carcinoma harboring susceptible FGFR3 alterations (NCCN.org).	detail...
IDH1 mutant	anaplastic astrocytoma	not applicable	N/A	Guideline	Diagnostic	IDH1 mutations aid in the diagnosis of grade III astrocytomas (NCCN.org).	detail...
FGFR3 fusion	oral cavity cancer	sensitive	Erdafitinib	Guideline	Actionable	Balversa (erdafitinib) is included in guidelines as subsequent-line therapy (category 2B) for patients with oral cavity cancer harboring FGFR mutations or fusions and with no alternative options (NCCN.org).	detail...
NTRK2 fusion	pilocytic astrocytoma	sensitive	Repotrectinib	Guideline	Actionable	Augtyro (repotrectinib) is included in guidelines (category 2B) for patients with recurrent or progressive circumscribed glioma, including pilocytic astrocytoma, harboring an NTRK fusion (NCCN.org).	detail...
NTRK1 fusion	intrahepatic cholangiocarcinoma	sensitive	Entrectinib	Guideline	Actionable	Rozlytrek (entrectinib) is included in guidelines as primary and subsequent-line therapy for patients with unresectable or metastatic biliary tract cancer harboring an NTRK fusion, including intrahepatic cholangiocarcinoma (NCCN.org).	detail...
BRAF V600E	esophagus squamous cell carcinoma	sensitive	Dabrafenib + Trametinib	Guideline	Actionable	Tafinlar (dabrafenib) and Mekinist (trametinib) combination therapy is included in guidelines as second-line or subsequent therapy for patients with locally advanced, recurrent, or metastatic esophageal squamous cell carcinoma harboring BRAF V600E (NCCN.org).	detail...
NTRK1 fusion	hepatocellular carcinoma	sensitive	Repotrectinib	Guideline	Actionable	Augtyro (repotrectinib) is included in guidelines for patients with hepatocellular carcinoma harboring an NTRK fusion (NCCN.org).	detail...
NTRK1 fusion	endometrial carcinoma	sensitive	Repotrectinib	Guideline	Actionable	Augtyro (repotrectinib) is included in guidelines as a second-line or subsequent-line therapy for patients with recurrent endometrial carcinoma harboring an NTRK fusion (NCCN.org).	detail...
MLH1 negative	hypopharynx cancer	sensitive	Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab) is included in guidelines as first- and subsequent-line therapy for patients with mismatch repair deficient (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) recurrent, unresectable, or metastatic hypopharynx cancer (NCCN.org).	detail...
NTRK1 fusion	lung non-small cell carcinoma	sensitive	Repotrectinib	Guideline	Actionable	Augtyro (repotrectinib) is included in guidelines as first-line or subsequent therapy for patients with advanced or metastatic non-small cell lung cancer harboring an NTRK1 fusion (NCCN.org).	detail...
BRAF V600X	skin melanoma	sensitive	Cobimetinib + Vemurafenib	Guideline	Actionable	Zelboraf (vemurafenib) and Cotellic (cobimetinib) combination therapy is included in guidelines as a second-line or subsequent therapy for patients with metastatic or unresectable cutaneous melanoma harboring a BRAF V600 activating mutation (NCCN.org).	detail...
ALK fusion	Erdheim-Chester disease	sensitive	Lorlatinib	Guideline	Actionable	Lorbrena (lorlatinib) is included in guidelines as first-line or subsequent-line therapy for patients with Erdheim-Chester disease harboring ALK fusions (NCCN.org).	detail...
ABL1 rearrange	B-cell acute lymphoblastic leukemia	not applicable	N/A	Guideline	Prognostic	ABL1 rearrangements are associated with a poor prognosis in patients with B-cell acute lymphoblastic leukemia (NCCN.org).	detail...
MSH6 negative	Adenocarcinoma of Unknown Primary	sensitive	Dostarlimab-gxly	Guideline	Actionable	Jemperli (dostarlimab-gxly) is included in guidelines for patients with adenocarcinoma of unknown primary with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
MLH1 negative	esophagus squamous cell carcinoma	sensitive	Fluorouracil + Oxaliplatin + Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab), in combination with Adrucil (fluorouracil) and Eloxatin (oxaliplatin) is included in guidelines as first-line therapy for patients with unresectable locally advanced, recurrent, or metastatic esophagus squamous cell carcinoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
MLH1 negative	gastroesophageal junction adenocarcinoma	sensitive	Ipilimumab + Nivolumab	Guideline	Actionable	Opdivo (nivolumab), in combination with Yervoy (ipilimumab), is included in guidelines as first-line, second-line, or subsequent therapy for patients with unresectable locally advanced, recurrent, or metastatic gastroesophageal junction adenocarcinoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
ALK rearrange	anaplastic large cell lymphoma	sensitive	Crizotinib	Guideline	Actionable	Xalkori (crizotinib) is included in guidelines as second-line and subsequent therapy for patients with anaplastic large cell lymphoma harboring ALK rearrangements (NCCN.org).	detail...
CDKN2A mutant	pancreatic cancer	not applicable	N/A	Guideline	Risk Factor	Germline mutations in CDKN2A results in familial malignant melanoma syndrome, which is associated with increased risk of developing pancreatic cancer (NCCN.org).	detail...
ATM mutant	chronic lymphocytic leukemia/small lymphocytic lymphoma	not applicable	N/A	Guideline	Prognostic	ATM mutations are associated with shorter time to first treatment, progression-free survival, time to next treatment, and overall survival with chemoimmunotherapy compared to wild-type ATM in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (NCCN.org).	detail...
NTRK2 fusion	anaplastic astrocytoma	sensitive	Larotrectinib	Guideline	Actionable	Vitrakvi (larotrectinib) is included in guidelines for patients with recurrent anaplastic gliomas harboring an NTRK fusion, including anaplastic astrocytoma (NCCN.org).	detail...
MLH1 negative	colon cancer	sensitive	Ipilimumab + Nivolumab	Guideline	Actionable	Opdivo (nivolumab), in combination with Yervoy (ipilimumab), is included in guidelines as primary or subsequent therapy for patients with advanced or metastatic colon cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
NTRK2 fusion	appendix adenocarcinoma	sensitive	Larotrectinib	Guideline	Actionable	Vitrakvi (larotrectinib) is included in guidelines (category 2A) as second-line or subsequent therapy for patients with advanced or metastatic appendiceal adenocarcinoma harboring an NTRK fusion (NCCN.org).	detail...
FGFR2 act mut	breast cancer	sensitive	Erdafitinib	Guideline	Actionable	Balversa (erdafitinib) is included in guidelines for patients with stage IV (M1) breast cancer harboring FGFR fusion or mutations (category 2B) (NCCN.org).	detail...
MSH6 negative	small intestine adenocarcinoma	sensitive	Atezolizumab + Capecitabine + Oxaliplatin	Guideline	Actionable	Tecentriq (atezolizumab) in combination with Xeloda (capecitabine) and Eloxatin (oxaliplatin) is included in guidelines as adjuvant therapy (category 2A) for patients with small bowel adenocarcinoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MSH6, MSH2, MLH1, or PMS2 expression by IHC) (NCCN.org).	detail...
NTRK1 fusion	papillary thyroid carcinoma	sensitive	Repotrectinib	Guideline	Actionable	Augtyro (repotrectinib) is included in guidelines for patients with RAI-refractory papillary thyroid carcinoma harboring an NTRK fusion with progressive or symptomatic disease (NCCN.org).	detail...
FLT3 exon23	acute myeloid leukemia	sensitive	Midostaurin	Guideline	Actionable	Rydapt (midostaurin) is included in guidelines as maintenance therapy for patients with acute myeloid leukemia harboring a mutation in the FLT3 tyrosine kinase domain (exons 14-23) (NCCN.org).	detail...
TP53 mutant	chronic lymphocytic leukemia/small lymphocytic lymphoma	sensitive	Ibrutinib + Venetoclax	Guideline	Actionable	Venclexta (venetoclax) combined with Imbruvica (ibrutinib) is included in guidelines as first-line (category 2A) and second-line or subsequent therapy (category 2B) for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with a TP53 mutation (NCCN.org).	detail...
MLH1 negative	rectum cancer	sensitive	Nivolumab	Guideline	Actionable	Opdivo (nivolumab) is included in guidelines as a primary therapy for advanced or metastatic rectum cancer patients with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
BRAF wild-type	rectum cancer	predicted - sensitive	Panitumumab	Guideline	Actionable	Vectibix (panitumumab) is included in guidelines for patients with advanced or metastatic rectal cancer that is BRAF wild-type, KRAS wild-type, and NRAS wild-type (NCCN.org).	detail...
TP53 mutant	chronic lymphocytic leukemia/small lymphocytic lymphoma	sensitive	Rituximab + Venetoclax	Guideline	Actionable	Venclexta (venetoclax) combined with Rituxan (rituximab) is included in guidelines as second-line or subsequent therapy (category 1) for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with a TP53 mutation (NCCN.org).	detail...
MLH1 mutant	small intestine adenocarcinoma	not applicable	N/A	Guideline	Risk Factor	Lynch syndrome results from germline mutations in DNA mismatch repair genes including MLH1, MSH2, MSH6, and PMS2, and is associated with increased risk of developing small bowel adenocarcinoma (NCCN.org).	detail...
NTRK1 fusion	ovary epithelial cancer	sensitive	Repotrectinib	Guideline	Actionable	Augtyro (repotrectinib) is included in guidelines as systemic therapy for patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer harboring an NTRK fusion (NCCN.org).	detail...
FLT3 exon 15 ins	acute myeloid leukemia	sensitive	Cytarabine + Daunorubicin + Quizartinib	Guideline	Actionable	Vanflyta (quizartinib) in combination with Cerubidine (daunorubicin) and Cytosar-U (cytarabine) is included in guidelines for patients with acute myeloid leukemia harboring a FLT3 internal tandem duplication (FLT3-ITD) mutation (NCCN.org).	detail...
RET fusion	hepatocellular carcinoma	sensitive	Selpercatinib	Guideline	Actionable	Retevmo (selpercatinib) is included in guidelines as subsequent-line therapy (category 2B) for patients with hepatocellular carcinoma harboring RET fusions (NCCN.org).	detail...
ABL1 rearrange	myeloid neoplasm	sensitive	Ponatinib	Guideline	Actionable	Iclusig (ponatinib) is included in guidelines for patients with a myeloid/lymphoid neoplasm with eosinophilia harboring an ABL1 rearrangement (NCCN.org).	detail...
MSH6 negative	rectum cancer	sensitive	Penpulimab-kcqx	Guideline	Actionable	Penpulimab-kcqx (AK105) is included in guidelines (category 2A) for patients with advanced or metastatic rectal cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MSH6, MSH2, MLH1, or PMS2 expression by IHC) (NCCN.org).	detail...
NRAS exon2	rectum cancer	resistant	Panitumumab	Guideline	Actionable	Vectibix (panitumumab) is not indicated for use in rectum cancer patients with NRAS exon 2 mutations (NCCN.org).	detail...
TP53 loss	chronic lymphocytic leukemia/small lymphocytic lymphoma	sensitive	Zanubrutinib	Guideline	Actionable	Brukinsa (zanubrutinib) is included in guidelines as first-line therapy and second line therapy (category 1) and subsequent therapy for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with TP53 loss (NCCN.org).	detail...
MLH1 negative	rectum cancer	sensitive	Retifanlimab	Guideline	Actionable	Zynyz (retifanlimab) is included in guidelines (category 2A) for patients with advanced or metastatic rectal cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
TP53 loss	chronic lymphocytic leukemia/small lymphocytic lymphoma	sensitive	Acalabrutinib	Guideline	Actionable	Calquence (acalabrutinib) is included in the guidelines as first-line (category 2A) and second-line or subsequent therapy (category 1) for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with TP53 loss (NCCN.org).	detail...
TP53 mutant	chronic lymphocytic leukemia/small lymphocytic lymphoma	sensitive	Acalabrutinib + Obinutuzumab + Venetoclax	Guideline	Actionable	The combination of Venclexta (venetoclax), Gazyva (obinutuzumab), and Calquence (acalabrutinib) is included in guidelines as first-line therapy for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with a TP53 mutation (NCCN.org).	detail...
NTRK2 fusion	salivary gland cancer	sensitive	Larotrectinib	Guideline	Actionable	Vitrakvi (larotrectinib) is included in guidelines for patients with NTRK2 fusion-positive salivary gland tumors with distant metastases (NCCN.org).	detail...
MSH6 negative	penile cancer	sensitive	Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab) is included in guidelines as subsequent-line systemic therapy for metastatic/recurrent penile cancer patients with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
MLH1 negative	rectum cancer	sensitive	Durvalumab	Guideline	Actionable	Imfinzi (durvalumab) is included in guidelines (category 2A) for patients with advanced or metastatic rectal cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, MSH2, MSH6, or PMS2 expression by IHC) (NCCN.org).	detail...
NTRK1 fusion	cervical cancer	sensitive	Larotrectinib	Guideline	Actionable	Vitrakvi (larotrectinib) is included in guidelines as second-line or subsequent therapy (category 2A) for patients with recurrent or metastatic cervical cancer harboring an NTRK fusion (NCCN.org).	detail...
FLT3 exon 15 ins	acute myeloid leukemia	sensitive	Sorafenib	Guideline	Actionable	Nexavar (sorafenib) is included in guidelines as maintenance therapy for patients with acute myeloid leukemia harboring a FLT3 internal tandem duplication (FLT3-ITD) mutation (NCCN.org).	detail...
IDH2 mutant	myelodysplastic syndrome	sensitive	Enasidenib	Guideline	Actionable	Idhifa (enasidenib) is included in guidelines (category 2A) for patients with myelodysplastic syndrome harboring an IDH2 mutation (NCCN.org).	detail...
MSH6 mutant	adrenocortical carcinoma	not applicable	N/A	Guideline	Risk Factor	Lynch syndrome results from germline mutations in DNA mismatch repair genes including MLH1, MSH2, MSH6, and PMS2, and is associated with increased risk of developing adrenocortical carcinoma (NCCN.org).	detail...
ALK rearrange ALK L1196M	lung non-small cell carcinoma	sensitive	Lorlatinib	Guideline	Actionable	Lorbrena (lorlatinib) is included in guidelines as subsequent therapy for patients with advanced or metastatic ALK-rearranged non-small cell lung cancer harboring ALK L1196M (NCCN.org).	detail...
NTRK2 fusion	cervical cancer	sensitive	Larotrectinib	Guideline	Actionable	Vitrakvi (larotrectinib) is included in guidelines as second-line or subsequent therapy (category 2A) for patients with recurrent or metastatic cervical cancer harboring an NTRK fusion (NCCN.org).	detail...
ABL1 rearrange	myeloid neoplasm	sensitive	Nilotinib	Guideline	Actionable	Tasigna (nilotinib) is included in guidelines as a preferred regimen for patients with a myeloid/lymphoid neoplasm with eosinophilia harboring an ABL1 rearrangement (NCCN.org).	detail...
BRAF fusion	pleomorphic xanthoastrocytoma	sensitive	Tovorafenib	Guideline	Actionable	Ojemda (tovorafenib) is included in guidelines (category 2A) for patients with recurrent or progressive circumscribed glioma, including pleomorphic xanthoastrocytoma, harboring BRAF fusions, rearrangements, or BRAF V600 mutations (NCCN.org).	detail...
FLT3 exon18	acute myeloid leukemia	sensitive	Midostaurin	Guideline	Actionable	Rydapt (midostaurin) is included in guidelines as maintenance therapy for patients with acute myeloid leukemia harboring a mutation in the FLT3 tyrosine kinase domain (exons 14-23) (NCCN.org).	detail...
ALK rearrange	anaplastic large cell lymphoma	not applicable	N/A	Guideline	Prognostic	The presence of ALK rearrangement is associated with a favorable prognosis in patients with anaplastic large cell lymphoma (NCCN.org).	detail...
TP53 loss	chronic lymphocytic leukemia/small lymphocytic lymphoma	not applicable	N/A	Guideline	Prognostic	Loss of TP53 is associated with a poor prognosis in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (NCCN.org).	detail...
MLH1 negative	follicular thyroid carcinoma	sensitive	Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab) is included in guidelines for patients with follicular thyroid carcinoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) after progression on prior treatment (NCCN.org).	detail...
RET C630X	medullary thyroid carcinoma	not applicable	N/A	Guideline	Risk Factor	Germline RET C630X mutations result in multiple endocrine neoplasia, type 2A (MEN 2A), which is associated with high risk of developing thyroid medullary carcinoma (NCCN.org).	detail...
ALK fusion	Erdheim-Chester disease	sensitive	Brigatinib	Guideline	Actionable	Alunbrig (brigatinib) is included in guidelines as first-line or subsequent-line therapy for patients with Erdheim-Chester disease harboring ALK fusions (NCCN.org).	detail...
JAK2 V617F	myelofibrosis	not applicable	N/A	Guideline	Prognostic	JAK2 V617F is associated with intermediate prognosis and higher risk of thrombosis when compared to the presence of CALR mutations in patients with primary myelofibrosis (NCCN.org).	detail...
BRAF V600E	glioblastoma	sensitive	Dabrafenib + Trametinib	Guideline	Actionable	Combination of Mekinist (trametinib) and Tafinlar (dabrafenib) is included in guidelines for patients with recurrent glioblastoma harboring BRAF V600E (NCCN.org).	detail...
MSH6 negative	rectum cancer	sensitive	Retifanlimab	Guideline	Actionable	Zynyz (retifanlimab) is included in guidelines (category 2A) for patients with advanced or metastatic rectal cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
MSH6 negative	endometrial carcinoma	sensitive	Nivolumab	Guideline	Actionable	Opdivo (nivolumab) is included in guidelines as a second-line or subsequent-line therapy for patients with high microsatellite instability (MSI-H) or mismatch repair deficient (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) recurrent endometrial carcinoma (NCCN.org).	detail...
FGFR3 act mut	oropharynx cancer	sensitive	Erdafitinib	Guideline	Actionable	Balversa (erdafitinib) is included in guidelines as subsequent-line therapy (category 2B) for patients with oropharynx cancer harboring FGFR mutations or fusions and with no alternative options (NCCN.org).	detail...
BRAF V600E	rectum cancer	sensitive	Capecitabine + Encorafenib + Oxaliplatin + Panitumumab	Guideline	Actionable	Braftovi (encorafenib) in combination with Vectibix (panitumumab) and CAPEOX is included in guidelines as an initial therapy (category 2A) for patients with advanced or metastatic rectal cancer harboring BRAF V600E (NCCN.org).	detail...
MSH6 negative	prostate adenocarcinoma	sensitive	Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab) is included in guidelines as a second-line therapy for patients with advanced or metastatic prostate adenocarcinoma with deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
BRAF V600E	oncocytic carcinoma of the thyroid	sensitive	Dabrafenib	Guideline	Actionable	Tafinlar (dabrafenib) is included in guidelines for patients with RAI-refractory oncocytic thyroid carcinoma harboring BRAF V600E for whom clinical trials or other systemic therapies are not available or appropriate (category 2B) (NCCN.org).	detail...
MLH1 negative	esophagus squamous cell carcinoma	sensitive	Ipilimumab + Nivolumab	Guideline	Actionable	Opdivo (nivolumab), in combination with Yervoy (ipilimumab), is included in guidelines as first-line, second-line, or subsequent therapy for patients with unresectable locally advanced, recurrent, or metastatic esophagus squamous cell carcinoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
FGFR1 rearrange	myeloid and lymphoid neoplasms associated with FGFR1 abnormalities	sensitive	Ponatinib	Guideline	Actionable	Iclusig (ponatinib) is included in guidelines for patients with a myeloid/lymphoid neoplasm with eosinophilia harboring an FGFR1 rearrangement (NCCN.org).	detail...
BRAF V600K	skin melanoma	sensitive	Dabrafenib	Guideline	Actionable	Tafinlar (dabrafenib) therapy is included in guidelines for cutaneous melanoma patients with unresectable or metastatic disease harboring BRAF V600 activating mutations, such as BRAF V600K, in cases where BRAF/MEK inhibitor combination therapy is contraindicated (NCCN.org).	detail...
PTEN mutant	breast cancer	not applicable	N/A	Guideline	Risk Factor	Germline PTEN mutations result in Cowden syndrome, which is associated with increased risk of developing breast cancer (NCCN.org).	detail...
NTRK1 fusion	gastrointestinal stromal tumor	sensitive	Larotrectinib	Guideline	Actionable	Vitrakvi (larotrectinib) is included in guidelines as neoadjuvant therapy for patients with resectable disease and as first-line systemic therapy for patients with unresectable or metastatic gastrointestinal stromal tumor (GIST) harboring NTRK fusions (NCCN.org).	detail...
FLT3 exon15	acute myeloid leukemia	sensitive	Midostaurin	Guideline	Actionable	Rydapt (midostaurin) is included in guidelines as maintenance therapy for patients with acute myeloid leukemia harboring a mutation in the FLT3 tyrosine kinase domain (exons 14-23) (NCCN.org).	detail...
FGFR2 rearrange	intrahepatic cholangiocarcinoma	sensitive	Futibatinib	Guideline	Actionable	Lytgobi (futibatinib) is included in guidelines as subsequent-line therapy (category 2A) for patients with cholangiocarcinoma harboring an FGFR2 fusion or rearrangement (NCCN.org).	detail...
MLH1 negative	stomach cancer	sensitive	Capecitabine + Nivolumab + Oxaliplatin	Guideline	Actionable	Opdivo (nivolumab), in combination with Xeloda (capecitabine) and Eloxatin (oxaliplatin) is included in guidelines as first-line therapy for patients with unresectable locally advanced, recurrent, or metastatic gastric cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
FLT3 exon 14 ins	acute myeloid leukemia	sensitive	Cytarabine + Daunorubicin + Quizartinib	Guideline	Actionable	Vanflyta (quizartinib) in combination with Cerubidine (daunorubicin) and Cytosar-U (cytarabine) is included in guidelines for patients with acute myeloid leukemia harboring a FLT3 internal tandem duplication (FLT3-ITD) mutation (NCCN.org).	detail...
MSH6 mutant	colon cancer	not applicable	N/A	Guideline	Risk Factor	Lynch syndrome results from germline mutations in DNA mismatch repair genes including MLH1, MSH2, MSH6, and PMS2, and is associated with increased risk of developing colon cancer (NCCN.org).	detail...
RET fusion	small intestine adenocarcinoma	sensitive	Selpercatinib	Guideline	Actionable	Retevmo (selpercatinib) is included in guidelines for patients with metastatic small bowel adenocarcinoma with RET fusion (NCCN.org).	detail...
RET fusion	salivary gland cancer	sensitive	Selpercatinib	Guideline	Actionable	Retevmo (selpercatinib) is included in guidelines (category 2A) for patients with recurrent, unresectable, or metastatic salivary gland tumors harboring RET fusions (NCCN.org).	detail...
IDH1 act mut	malignant astrocytoma	sensitive	Ivosidenib	Guideline	Actionable	Tibsovo (ivosidenib) is included in guidelines for patients with WHO grade 2 astrocytoma harboring an IDH1 activating mutation with residual/measurable disease or as adjuvant treatment after surgery/biopsy or recurrent or progressive disease and WHO grade 3 or 4 with recurrent or progressive disease or WHO grade 3 as adjuvant treatment (category 2B) (NCCN.org).	detail...
FGFR2 act mut	lung non-small cell carcinoma	sensitive	Erdafitinib	Guideline	Actionable	Balversa (erdafitinib) is included in guidelines for patients with metastatic non-small cell lung cancer harboring oncogenic or likely oncogenic FGFR alterations (NCCN.org).	detail...
MLH1 negative	extrahepatic bile duct carcinoma	sensitive	Dostarlimab-gxly	Guideline	Actionable	Jemperli (dostarlimab-gxly) is included in guidelines as subsequent therapy (category 2B) for patients with biliary tract cancer with deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC), including extrahepatic cholangiocarcinoma (NCCN.org).	detail...
TP53 loss	chronic lymphocytic leukemia/small lymphocytic lymphoma	sensitive	Ibrutinib	Guideline	Actionable	Imbruvica (ibrutinib) is included in guidelines as first-line therapy and second-line or subsequent therapy for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with TP53 loss (NCCN.org).	detail...
FGFR2 act mut	supraglottis cancer	sensitive	Erdafitinib	Guideline	Actionable	Balversa (erdafitinib) is included in guidelines as subsequent-line therapy (category 2B) for patients with supraglottic larynx cancer harboring FGFR mutations or fusions and with no alternative options (NCCN.org).	detail...
IDH2 mutant	acute myeloid leukemia	sensitive	Azacitidine + Venetoclax	Guideline	Actionable	Venclexta (venetoclax) in combination with Vidaza (azacitidine) is included in guidelines for adult patients with acute myeloid leukemia harboring an IDH2 mutation (NCCN.org).	detail...
JAK2 mutant	childhood B-cell acute lymphoblastic leukemia	not applicable	N/A	Guideline	Prognostic	JAK2 mutations are associated with a poor prognosis in pediatric patients with B-cell acute lymphoblastic leukemia (NCCN.org).	detail...
NTRK2 fusion	high grade glioma	sensitive	Larotrectinib	Guideline	Actionable	Vitrakvi (larotrectinib) is included in guidelines as adjuvant therapy for pediatric patients with diffuse high-grade gliomas harboring NTRK fusions, or as a preferred regimen for patients with recurrent or progressive disease (NCCN.org).	detail...
IDH1 mutant	acute myeloid leukemia	sensitive	Cytarabine + Venetoclax	Guideline	Actionable	Venclexta (venetoclax) in combination with Cytosar-U (cytarabine) is included in guidelines for adult patients with acute myeloid leukemia harboring an IDH1 mutation (NCCN.org).	detail...
MLH1 negative	appendix adenocarcinoma	sensitive	Ipilimumab + Nivolumab	Guideline	Actionable	Opdivo (nivolumab) in combination with Yervoy (ipilimumab) is included in guidelines (category 2A) for patients with advanced or metastatic appendiceal adenocarcinoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
NTRK2 fusion	Adenocarcinoma of Unknown Primary	sensitive	Repotrectinib	Guideline	Actionable	Augtyro (repotrectinib) is included in guidelines for patients with adenocarcinoma of unknown primary harboring NTRK2 fusions (NCCN.org).	detail...
RET fusion	ampulla of Vater adenocarcinoma	sensitive	Selpercatinib	Guideline	Actionable	Retevmo (selpercatinib) is included in guidelines as first-line or subsequent therapy for patients with metastatic ampullary adenocarcinoma harboring RET fusions (NCCN.org).	detail...
ALK rearrange	inflammatory myofibroblastic tumor	sensitive	Alectinib	Guideline	Actionable	Alecensa (alectinib) is included in guidelines as first-line therapy for patients with advanced, recurrent, metastatic, or inoperable inflammatory myofibroblastic tumor harboring ALK translocations (NCCN.org).	detail...
MLH1 negative	small intestine adenocarcinoma	sensitive	Penpulimab-kcqx	Guideline	Actionable	Penpulimab-kcqx (AK105) is included in guidelines as systemic therapy (category 2A) for patients with advanced or metastatic small bowel adenocarcinoma with deficient mismatch repair (dMMR, often defined by the loss of MLH1, MSH2, MSH6, or PMS2 expression by IHC) (NCCN.org).	detail...
NTRK2 fusion	oncocytic carcinoma of the thyroid	sensitive	Repotrectinib	Guideline	Actionable	Augtyro (repotrectinib) is included in guidelines for patients with RAI-refractory oncocytic thyroid carcinoma harboring an NTRK fusion with progressive or symptomatic disease (NCCN.org).	detail...
BRAF V600E	pleomorphic xanthoastrocytoma	sensitive	Dabrafenib + Trametinib	Guideline	Actionable	Mekinist (trametinib) and Tafinlar (dabrafenib) combination therapy is included in guidelines as an adjuvant treatment for patients with pleomorphic xanthoastrocytoma harboring BRAF V600E (NCCN.org).	detail...
NTRK1 fusion	esophagus squamous cell carcinoma	sensitive	Larotrectinib	Guideline	Actionable	Vitrakvi (larotrectinib) is included in guidelines as second-line or subsequent therapy for patients with unresectable locally advanced, recurrent, or metastatic esophageal squamous cell carcinoma with an NTRK fusion (NCCN.org).	detail...
MSH6 negative	appendix adenocarcinoma	sensitive	Retifanlimab	Guideline	Actionable	Zynyz (retifanlimab) is included in guidelines (category 2A) for patients with advanced or metastatic appendiceal adenocarcinoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
CBL mutant	myelofibrosis	not applicable	N/A	Guideline	Prognostic	CBL mutations are associated with inferior overall survival in patients with primary myelofibrosis (NCCN.org).	detail...
RET V804M RET E805K	medullary thyroid carcinoma	not applicable	N/A	Guideline	Risk Factor	Compound germline RET V804M and E805K mutations result in multiple endocrine neoplasia, type 2B (MEN 2B), which is associated with high risk of developing thyroid medullary carcinoma (NCCN.org).	detail...
NTRK1 fusion	Erdheim-Chester disease	sensitive	Entrectinib	Guideline	Actionable	Rozlytrek (entrectinib) is included in guidelines as first-line or subsequent-line therapy for patients with Erdheim-Chester disease harboring NTRK1 fusions (NCCN.org).	detail...
BRAF V600E	rectum cancer	sensitive	Cetuximab + Encorafenib	Guideline	Actionable	Braftovi (encorafenib) in combination with Erbitux (cetuximab) is included in guidelines as primary or subsequent therapy for patients with rectal cancer harboring BRAF V600E (NCCN.org).	detail...
MSH6 negative	endometrial carcinoma	sensitive	Tislelizumab	Guideline	Actionable	Tevimbra (tislelizumab) is included in guidelines as a second-line or subsequent-line therapy for patients with high microsatellite instability (MSI-H) or mismatch repair-deficient (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) recurrent endometrial carcinoma (NCCN.org).	detail...
MLH1 negative	gastroesophageal junction adenocarcinoma	sensitive	Fluorouracil + Nivolumab + Oxaliplatin	Guideline	Actionable	Opdivo (nivolumab), in combination with Adrucil (fluorouracil) and Eloxatin (oxaliplatin) is included in guidelines as first-line therapy for patients with unresectable locally advanced, recurrent, or metastatic gastroesophageal junction adenocarcinoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
FLT3 exon22	acute myeloid leukemia	sensitive	Cytarabine + Idarubicin + Midostaurin	Guideline	Actionable	Rydapt (midostaurin) in combination with Idarubicin and Cytosar-U (cytarabine) is included in guidelines for patients with acute myeloid leukemia harboring a mutation in the FLT3 tyrosine kinase domain (exons 14-23) (NCCN.org).	detail...
RET fusion	appendix adenocarcinoma	sensitive	Selpercatinib	Guideline	Actionable	Retevmo (selpercatinib) is included in guidelines (category 2A) as second-line or subsequent therapy for patients with advanced or metastatic appendiceal adenocarcinoma harboring RET fusions (NCCN.org).	detail...
TP53 mutant	mantle cell lymphoma	sensitive	Obinutuzumab + Venetoclax + Zanubrutinib	Guideline	Actionable	The combination of Brukinsa (zanubrutinib), Gazyva (obinutuzumab), and Venclexta (venetoclax) is included in guidelines as induction therapy for patients with mantle cell lymphoma harboring a TP53 mutation (NCCN.org).	detail...
FGFR1 fusion	oropharynx cancer	sensitive	Erdafitinib	Guideline	Actionable	Balversa (erdafitinib) is included in guidelines as subsequent-line therapy (category 2B) for patients with oropharynx cancer harboring FGFR mutations or fusions and with no alternative options (NCCN.org).	detail...
MLH1 mutant	adrenocortical carcinoma	not applicable	N/A	Guideline	Risk Factor	Lynch syndrome results from germline mutations in DNA mismatch repair genes including MLH1, MSH2, MSH6, and PMS2, and is associated with increased risk of developing adrenocortical carcinoma (NCCN.org).	detail...
BRAF V600E	skin melanoma	sensitive	Dabrafenib + Pembrolizumab + Trametinib	Guideline	Actionable	Tafinlar (dabrafenib) plus Mekinist (trametinib) in combination with an immune checkpoint inhibitor, such as Keytruda (pembrolizumab), is included in guidelines as second-line or subsequent therapy (category 2A) for patients with metastatic or unresectable cutaneous melanoma harboring a BRAF V600 mutation, such as BRAF V600E (NCCN.org).	detail...
TP53 mutant	chronic lymphocytic leukemia/small lymphocytic lymphoma	sensitive	Duvelisib	Guideline	Actionable	Copiktra (duvelisib) is included in guidelines for patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma with a TP53 mutation after prior BTK inhibitor-based and BCL2 inhibitor-containing regimens (NCCN.org).	detail...
RET fusion	gastroesophageal junction adenocarcinoma	sensitive	Selpercatinib	Guideline	Actionable	Retevmo (selpercatinib) is included in guidelines as second-line or subsequent therapy for patients with locally advanced, recurrent, or metastatic gastroesophageal junction adenocarcinoma harboring RET fusions (NCCN.org).	detail...
MSH6 negative	gastroesophageal junction adenocarcinoma	sensitive	Dostarlimab-gxly	Guideline	Actionable	Jemperli (dostarlimab-gxly) is included in guidelines as neoadjuvant, preferred first-line, second-line, or subsequent therapy for patients with unresectable locally advanced, recurrent, or metastatic gastroesophageal junction adenocarcinoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
MSH6 negative	rectum cancer	sensitive	Durvalumab	Guideline	Actionable	Imfinzi (durvalumab) is included in guidelines (category 2A) for patients with advanced or metastatic rectal cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MSH6, MSH2, MLH1, or PMS2 expression by IHC) (NCCN.org).	detail...
NTRK2 fusion	gastroesophageal junction adenocarcinoma	sensitive	Entrectinib	Guideline	Actionable	Rozlytrek (entrectinib) is included in guidelines as second-line or subsequent therapy for patients with unresectable locally advanced, recurrent, or metastatic gastroesophageal junction adenocarcinoma with an NTRK fusion (NCCN.org).	detail...
FLT3 exon19	acute myeloid leukemia	sensitive	Cytarabine + Idarubicin + Midostaurin	Guideline	Actionable	Rydapt (midostaurin) in combination with Idamycin (idarubicin) and Cytosar-U (cytarabine) is included in guidelines for patients with acute myeloid leukemia harboring a mutation in the FLT3 tyrosine kinase domain (exons 14-23) (NCCN.org).	detail...
NTRK2 fusion	pleomorphic xanthoastrocytoma	sensitive	Repotrectinib	Guideline	Actionable	Augtyro (repotrectinib) is included in guidelines (category 2B) for patients with recurrent or progressive circumscribed glioma, including pleomorphic xanthoastrocytoma, harboring an NTRK fusion (NCCN.org).	detail...
NTRK1 fusion	esophagus adenocarcinoma	sensitive	Entrectinib	Guideline	Actionable	Rozlytrek (entrectinib) is included in guidelines as second-line or subsequent therapy for patients with unresectable locally advanced, recurrent, or metastatic esophageal adenocarcinoma with an NTRK fusion (NCCN.org).	detail...
NTRK2 fusion	anaplastic oligodendroglioma	sensitive	Larotrectinib	Guideline	Actionable	Vitrakvi (larotrectinib) is included in guidelines for patients with recurrent anaplastic gliomas harboring an NTRK fusion, including anaplastic oligodendroglioma (NCCN.org).	detail...
MLH1 negative	colon cancer	sensitive	Atezolizumab + Fluorouracil + Leucovorin + Oxaliplatin	Guideline	Actionable	Tecentriq (atezolizumab) in combination with Adrucil (fluorouracil), Wellcovorin (leucovorin), and Eloxatin (oxaliplatin) is included in guidelines as adjuvant therapy for patients with colon cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
BRAF V600E	gastroesophageal junction adenocarcinoma	sensitive	Dabrafenib + Trametinib	Guideline	Actionable	Tafinlar (dabrafenib) and Mekinist (trametinib) combination therapy is included in guidelines as second-line or subsequent therapy for patients with locally advanced, recurrent, or metastatic gastroesophageal junction adenocarcinoma harboring BRAF V600E (NCCN.org).	detail...
BRAF V600E	Erdheim-Chester disease	sensitive	Vemurafenib	Guideline	Actionable	Zelboraf (vemurafenib) is included in guidelines as preferred first-line or subsequent-line therapy for patients with Erdheim-Chester disease harboring BRAF V600E (NCCN.org).	detail...
TP53 mutant	chronic lymphocytic leukemia/small lymphocytic lymphoma	sensitive	Obinutuzumab + Venetoclax	Guideline	Actionable	The combination of Venclexta (venetoclax) and Gazyva (obinutuzumab) is included in guidelines as first-line therapy for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with a TP53 mutation (NCCN.org).	detail...
MSH6 negative	ampulla of Vater adenocarcinoma	sensitive	Dostarlimab-gxly	Guideline	Actionable	Jemperli (dostarlimab-gxly) is included in guidelines as subsequent therapy for metastatic ampullary adenocarcinoma patients with deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
FLT3 exon23	acute myeloid leukemia	sensitive	Cytarabine + Daunorubicin + Midostaurin	Guideline	Actionable	Rydapt (midostaurin), in combination with Cerubidine (daunorubicin) and Cytosar-U (cytarabine), is included in guidelines for patients with acute myeloid leukemia harboring a mutation in the FLT3 tyrosine kinase domain (exons 14-23) (NCCN.org).	detail...
NTRK2 fusion	small intestine adenocarcinoma	sensitive	Larotrectinib	Guideline	Actionable	Vitrakvi (larotrectinib) is included in guidelines for patients with metastatic small bowel adenocarcinoma with an NTRK fusion (NCCN.org).	detail...
NRAS mutant	Erdheim-Chester disease	sensitive	Trametinib	Guideline	Actionable	Mekinist (trametinib) is included in guidelines as first-line or subsequent-line therapy for patients with Erdheim-Chester disease harboring mutations in the MAPK pathway such as ARAF, NRAS, KRAS, MAP2K1/2, PIK3CA, or with no detectable mutations, or for whom testing is not available (NCCN.org).	detail...
ALK rearrange	lung non-small cell carcinoma	sensitive	Crizotinib	Guideline	Actionable	Xalkori (crizotinib) is included in guidelines as first-line therapy (category 1) for patients with ALK-rearranged advanced or metastatic non-small cell lung cancer, and as a subsequent therapy after asymptomatic progression on Xalkori (crizotinib) treatment (NCCN.org).	detail...
MSH6 negative	endometrial carcinoma	sensitive	Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab) is included in guidelines as first-line or subsequent-line therapy for patients with recurrent or metastatic endometrial carcinoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
NRAS Q61X	myelodysplastic syndrome	not applicable	N/A	Guideline	Prognostic	NRAS Q61X is associated with a poor prognosis in patients with myelodysplastic syndrome (NCCN.org).	detail...
NTRK2 fusion	colon cancer	sensitive	Larotrectinib	Guideline	Actionable	Vitrakvi (larotrectinib) is included in guidelines for advanced or metastatic colon cancer patients with an NTRK fusion (NCCN.org).	detail...
NTRK2 fusion	neuroendocrine tumor	sensitive	Larotrectinib	Guideline	Actionable	Vitrakvi (larotrectinib) is included in guidelines for patients with unresectable or metastatic extrapulmonary poorly differentiated neuroendocrine carcinoma, large or small cell carcinoma, or mixed neuroendocrine/non-neuroendocrine neoplasms harboring an NTRK fusion who have progressed on or following prior treatment (NCCN.org).	detail...
FLT3 exon23	acute myeloid leukemia	sensitive	Cytarabine + Midostaurin	Guideline	Actionable	Rydapt (midostaurin) in combination with Cytosar-U (cytarabine) is included in guidelines as consolidation therapy for patients with acute myeloid leukemia harboring a mutation in the FLT3 tyrosine kinase domain (exons 14-23) (NCCN.org).	detail...
NTRK2 fusion	oncocytic carcinoma of the thyroid	sensitive	Larotrectinib	Guideline	Actionable	Vitrakvi (larotrectinib) is included in guidelines for patients with RAI-refractory oncocytic thyroid carcinoma harboring an NTRK fusion with progressive or symptomatic disease (NCCN.org).	detail...
NTRK2 fusion	skin melanoma	sensitive	Entrectinib	Guideline	Actionable	Rozlytrek (entrectinib) therapy is included in guidelines for patients with metastatic or unresectable cutaneous melanoma harboring an NTRK fusion (NCCN.org).	detail...
IDH1 mutant	oligodendroglioma	not applicable	N/A	Guideline	Diagnostic	IDH1 mutations aid in the diagnosis of oligodendrogliomas (NCCN.org).	detail...
FLT3 exon16	acute myeloid leukemia	sensitive	Midostaurin	Guideline	Actionable	Rydapt (midostaurin) is included in guidelines as maintenance therapy for patients with acute myeloid leukemia harboring a mutation in the FLT3 tyrosine kinase domain (exons 14-23) (NCCN.org).	detail...
ABL1 rearrange	myeloid neoplasm	sensitive	Bosutinib	Guideline	Actionable	Bosulif (bosutinib) is included in guidelines for patients with a myeloid/lymphoid neoplasm with eosinophilia harboring an ABL1 rearrangement (NCCN.org).	detail...
RET fusion	extrahepatic bile duct carcinoma	sensitive	Pralsetinib	Guideline	Actionable	Gavreto (pralsetinib) is included in guidelines as primary (category 2B) and subsequent-line therapy (category 2B) for patients with unresectable or metastatic biliary tract cancer harboring RET fusions, including extrahepatic cholangiocarcinoma (NCCN.org).	detail...
MLH1 negative	vulva squamous cell carcinoma	sensitive	Pembrolizumab	Guideline	Actionable	Keytruda (pembrolizumab) is included in guidelines as a second-line or subsequent therapy for patients with advanced or recurrent/metastatic MSI high or dMMR (often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) vulva squamous cell carcinoma (NCCN.org).	detail...
VHL inact mut	renal cell carcinoma	sensitive	Pazopanib	Guideline	Actionable	Votrient (pazopanib) is included in guidelines as systemic therapy for patients with renal cell carcinoma associated with Von Hippel-Lindau disease (NCCN.org).	detail...
MSH6 negative	stomach cancer	sensitive	Fluorouracil + Nivolumab + Oxaliplatin	Guideline	Actionable	Opdivo (nivolumab), in combination with Adrucil (fluorouracil) and Eloxatin (oxaliplatin) is included in guidelines as first-line therapy for patients with unresectable locally advanced, recurrent, or metastatic gastric cancer with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) (NCCN.org).	detail...
BRAF V600E	follicular thyroid carcinoma	sensitive	Vemurafenib	Guideline	Actionable	Zelboraf (vemurafenib) is included in guidelines for patients with RAI-refractory follicular thyroid carcinoma harboring BRAF V600E for whom clinical trials or other systemic therapies are not available or appropriate (category 2B) (NCCN.org).	detail...
MLH1 negative	pancreatic adenocarcinoma	sensitive	Dostarlimab-gxly	Guideline	Actionable	Jemperli (dostarlimab-gxly) is included in guidelines as subsequent therapy for patients with locally advanced, metastatic, or recurrent pancreatic adenocarcinoma with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) with good (ECOG 0-1), intermediate (ECOG 2) (category 2A), or poor (ECOG 3) (category 2B) performance status who have not received prior immunotherapy (NCCN.org).	detail...
IDH2 mutant	acute myeloid leukemia	sensitive	Azacitidine + Enasidenib	Guideline	Actionable	Idhifa (enasidenib) in combination with Vidaza (azacitidine) is included in guidelines (category 2B) for patients with acute myeloid leukemia harboring an IDH2 mutation (NCCN.org).	detail...
ALK rearrange	anaplastic large cell lymphoma	not applicable	N/A	Guideline	Diagnostic	ALK rearrangement aids in the diagnosis of anaplastic large cell lymphoma (NCCN.org).	detail...
TP53 mutant	mantle cell lymphoma	not applicable	N/A	Guideline	Prognostic	TP53 mutations are associated with poor prognosis in patients with mantle cell lymphoma who are treated with conventional therapy, including transplant (NCCN.org).	detail...

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