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Gene | KIT |
Variant | D816V |
Impact List | missense |
Protein Effect | gain of function |
Gene Variant Descriptions | KIT D816V lies within the tyrosine kinase domain 2 of the Kit protein (PMID: 19865100). D816V results in constitutive phosphorylation of Kit, activation of Stat5 signaling (PMID: 19865100, PMID: 18390729), induces mastocytosis and tumor formation in mice (PMID: 21148330) and confers resistance to Kit inhibitors (PMID: 22301675, PMID: 19164557). |
Associated Drug Resistance | Y |
Category Variants Paths |
KIT mutant KIT act mut KIT D816V KIT mutant KIT exon17 KIT D816X KIT D816V |
Transcript | NM_000222.3 |
gDNA | chr4:g.54733155A>T |
cDNA | c.2447A>T |
Protein | p.D816V |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_001385290.1 | chr4:g.54733155A>T | c.2447A>T | p.D816V | RefSeq | GRCh38/hg38 |
XM_017008179.1 | chr4:g.54733167A>T | c.2447A>T | p.D816V | RefSeq | GRCh38/hg38 |
NM_000222 | chr4:g.54733155A>T | c.2447A>T | p.D816V | RefSeq | GRCh38/hg38 |
NM_001385292.1 | chr4:g.54733167A>T | c.2447A>T | p.D816V | RefSeq | GRCh38/hg38 |
XM_005265741 | chr4:g.54733155A>T | c.2447A>T | p.D816V | RefSeq | GRCh38/hg38 |
XM_005265741.1 | chr4:g.54733155A>T | c.2447A>T | p.D816V | RefSeq | GRCh38/hg38 |
NM_001093772 | chr4:g.54733167A>T | c.2447A>T | p.D816V | RefSeq | GRCh38/hg38 |
NM_001093772.1 | chr4:g.54733167A>T | c.2447A>T | p.D816V | RefSeq | GRCh38/hg38 |
NM_000222.3 | chr4:g.54733155A>T | c.2447A>T | p.D816V | RefSeq | GRCh38/hg38 |
NM_001093772.2 | chr4:g.54733167A>T | c.2447A>T | p.D816V | RefSeq | GRCh38/hg38 |
XM_017008179 | chr4:g.54733167A>T | c.2447A>T | p.D816V | RefSeq | GRCh38/hg38 |
NM_000222.2 | chr4:g.54733155A>T | c.2447A>T | p.D816V | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
KIT D816V | hematologic cancer | sensitive | Crenolanib | Preclinical - Cell culture | Actionable | In a preclinical study, Crenolanib inhibited Kit phosphorylation and growth of transformed hematologic cells expressing KIT D816V in culture (PMID: 31309543). | 31309543 |
KIT D816V | acute myeloid leukemia | sensitive | Crenolanib | Preclinical - Cell culture | Actionable | In a preclinical study, Crenolanib inhibited Kit phosphorylation and growth of erythroleukemia cells expressing KIT D816V in culture (PMID: 31309543). | 31309543 |
KIT D816V | hematologic cancer | sensitive | Dasatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT D816V were sensitive to treatment with Sprycel (dasatinib) in culture, demonstrating reduced cell survival (PMID: 31182436). | 31182436 |
KIT D816V | systemic mastocytosis | resistant | Imatinib | FDA contraindicated | Actionable | Gleevec (imatinib) is not indicated for patients with aggressive systemic mastocytosis harboring KIT D816V (FDA.gov). | detail... |
KIT D816V | hematologic cancer | resistant | Imatinib | Preclinical | Actionable | In a preclinical study, a mouse myeloid cell line expressing KIT D816V demonstrated resistance to Gleevec (imatinib) in culture (PMID: 12481435). | 12481435 |
KIT D816V | Advanced Solid Tumor | resistant | Imatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Gleevec (imatinib) treatment did not inhibit proliferation of transformed cells expressing KIT D816V in culture (PMID: 30523507). | 30523507 |
KIT D816V | Advanced Solid Tumor | resistant | Imatinib | Preclinical | Actionable | In a preclinical study, transformed cells expressing KIT D816V demonstrated resistance to Gleevec (imatinib mesylate) in culture (PMID: 15790786). | 15790786 |
KIT D816V | Advanced Solid Tumor | resistant | Imatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT D816V were resistant to Gleevec (imatinib) treatment in culture (PMID: 35194937). | 35194937 |
KIT D816V | hematologic cancer | sensitive | Midostaurin | Preclinical - Cell culture | Actionable | In a preclinical study, Rydapt (midostaurin) inhibited Kit phosphorylation and growth of transformed hematologic cells expressing KIT D816V in culture (PMID: 31309543). | 31309543 |
KIT D816V | acute myeloid leukemia | sensitive | Midostaurin | Preclinical - Cell culture | Actionable | In a preclinical study, Rydapt (midostaurin) inhibited Kit phosphorylation and growth of erythroleukemia cells expressing KIT D816V in culture (PMID: 31309543). | 31309543 |
KIT D816V | Advanced Solid Tumor | sensitive | Midostaurin | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT D816V were sensitive to treatment with Rydapt (midostaurin) in culture, demonstrating decreased cell proliferation (PMID: 31270078). | 31270078 |
KIT D816V | Advanced Solid Tumor | decreased response | Nilotinib | Preclinical | Actionable | In a preclinical study, Tasigna (nilotinib) decreased viability of cells expressing KIT D816V in culture, but did not inhibit KIT phosphorylation or growth of KIT D816V-expressing tumors in mouse models (PMID: 20442311). | 20442311 |
KIT D816V | Advanced Solid Tumor | resistant | Ponatinib | Preclinical | Actionable | In a preclinical study, Iclusig (ponatinib) did not inhibit growth of transformed cells expressing KIT D816V in culture (PMID: 22301675). | 22301675 |
KIT D816V | hematologic cancer | resistant | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, Vanflyta (quizartinib) did not inhibit Kit phosphorylation or growth of transformed hematologic cells expressing KIT D816V in culture (PMID: 31309543). | 31309543 |
KIT D816V | acute myeloid leukemia | resistant | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, Vanflyta (quizartinib) did not inhibit Kit phosphorylation or growth of erythroleukemia cells expressing KIT D816V in culture (PMID: 31309543). | 31309543 |
KIT D816V | Advanced Solid Tumor | resistant | Quizartinib | Preclinical | Actionable | In a preclinical study, transformed cells expressing KIT D816V demonstrated resistance to Quizartinib in culture (PMID: 23497317). | 23497317 |
KIT D816V | Advanced Solid Tumor | resistant | Regorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT D816V were resistant to Stivarga (regorafenib) in culture (PMID: 31085175). | 31085175 |
KIT D816V | hematologic cancer | resistant | Sorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Nexavar (sorafenib) did not inhibit Kit phosphorylation or growth of transformed hematologic cells expressing KIT D816V in culture (PMID: 31309543). | 31309543 |
KIT D816V | hematologic cancer | resistant | Sorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed hematopoietic cells expressing KIT D816V demonstrated resistance to Nexavar (sorafenib) in culture (PMID: 17229632). | 17229632 |
KIT D816V | acute myeloid leukemia | resistant | Sorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Nexavar (sorafenib) did not inhibit Kit phosphorylation or growth of erythroleukemia cells expressing KIT D816V in culture (PMID: 31309543). | 31309543 |
KIT D816V | Advanced Solid Tumor | resistant | Sunitinib | Preclinical | Actionable | In a preclinical study, KIT D816V mutations demonstrated resistance to Sutent (sunitinib) in a biochemical assay (PMID: 19164557). | 19164557 |
KIT D816V | Advanced Solid Tumor | resistant | Sunitinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT D816V were resistant to treatment with Sutent (sunitinib) in culture (PMID: 24205792). | 24205792 |
KIT D816V | Advanced Solid Tumor | resistant | Cabozantinib | Preclinical | Actionable | In a preclinical study, transformed cells expressing KIT D816V demonstrated resistance to Cometriq (cabozantinib) in culture (PMID: 24205792). | 24205792 |
KIT D816V | systemic mastocytosis | not applicable | N/A | Guideline | Diagnostic | KIT D816V aids in the diagnosis of systemic mastocytosis (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... |
KIT D816V | Advanced Solid Tumor | sensitive | PLX9486 | Preclinical - Cell culture | Actionable | In a preclinical study, PLX9486 treatment inhibited proliferation of Gleevec (imatinib)-resistant transformed cells expressing KIT D816V in culture (PMID: 30523507). | 30523507 |
KIT D816V | hematologic cancer | predicted - sensitive | Gilteritinib | Preclinical - Cell culture | Actionable | In a preclinical study, Xospata (gilteritinib) demonstrated moderate inhibition of Kit phosphorylation and growth of transformed hematologic cells expressing KIT D816V in culture (PMID: 31309543). | 31309543 |
KIT D816V | acute myeloid leukemia | predicted - sensitive | Gilteritinib | Preclinical - Cell culture | Actionable | In a preclinical study, Xospata (gilteritinib) demonstrated moderate inhibition of Kit phosphorylation and growth of erythroleukemia cells expressing KIT D816V in culture (PMID: 31309543). | 31309543 |
KIT D816V | systemic mastocytosis | sensitive | Avapritinib | Phase II | Actionable | In a Phase II trial (PATHFINDER), Ayvakit (avapritinib) treatment resulted in an objective response rate of 75% (24/32) in evaluable patients (pts) with advanced systemic mastocytosis, at 10.4 mo median follow-up, 84% (52/62) of pts remained on study, with median overall survival (OS) not reached, median time to response of 2 mo, an estimated 12 mo OS of 87%, and KIT D816V allele reduction in 53% of pts (33/62) (AACR Annual Meeting, Apr 2021, Abstract CT023; NCT03580655). | detail... |
KIT D816V | hematologic cancer | sensitive | Avapritinib | Preclinical - Cell culture | Actionable | In a preclinical study, Ayvakit (avapritinib) inhibited Kit phosphorylation and growth of transformed hematologic cells expressing KIT D816V in culture (PMID: 31309543). | 31309543 |
KIT D816V | mast cell neoplasm | predicted - sensitive | Avapritinib | Phase I | Actionable | In a Phase I trial, patients with either aggressive systemic mastocytosis, mast cell leukemia, or systemic mastocytosis with an associated hematologic neoplasm harboring KIT D816V demonstrated a reduction in mast cell burden and a decrease in KIT D816V allelic fraction when treated with Ayvakit (avapritinib) (ASH Annual Meeting, Dec 2017, Plenary 2). | detail... |
KIT D816V | acute myeloid leukemia | sensitive | Avapritinib | Preclinical - Cell culture | Actionable | In a preclinical study, Ayvakit (avapritinib) inhibited Kit phosphorylation and growth of erythroleukemia cells expressing KIT D816V in culture (PMID: 31309543). | 31309543 |
KIT D816V | Advanced Solid Tumor | sensitive | Avapritinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT D816V were sensitive to treatment with Ayvakit (avapritinib) in culture, demonstrating decreased cell proliferation (PMID: 31270078). | 31270078 |
KIT D816V | Advanced Solid Tumor | resistant | Flumatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT D816V were resistant to treatment with Flumatinib in culture (PMID: 24205792). | 24205792 |
KIT D816V | acute myeloid leukemia | sensitive | Cytarabine + Dasatinib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with acute myeloid leukemia harboring KIT D816V achieved long-term remission and loss of KIT D816V following treatment with the combination of Sprycel (dasatinib) and Cytosar-U (cytarabine) (PMID: 18986703). | 18986703 |
KIT D816V | Advanced Solid Tumor | sensitive | Ripretinib | Preclinical - Cell culture | Actionable | In a preclinical study, Qinlock (ripretinib) inhibited proliferation of transformed cells expressing KIT D816V in culture (PMID: 31085175). | 31085175 |
KIT D816V | Advanced Solid Tumor | predicted - sensitive | BPR1J373 | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT D816V were sensitive to BPR1J373, demonstrating inhibition of Kit phosphorylation (PMID: 27512117). | 27512117 |
KIT D816V | hematologic cancer | sensitive | FF-10101 | Preclinical - Cell culture | Actionable | In a preclinical study, FF-10101, as compared to Quizartinib, inhibited cell proliferation of transformed 32Dcl3 murine myeloid cells expressing human Kit D816V (PMID: 29187377). | 29187377 |