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Gene | BRAF |
Variant | L597R |
Impact List | missense |
Protein Effect | gain of function |
Gene Variant Descriptions | BRAF L597R lies within the protein kinase domain of the Braf protein (UniProt.org). L597R results in activation of Braf as indicated by increased phosphorylation of Mek and Erk in cell culture (PMID: 22798288, PMID: 26343582), is associated with Erk activation in a patient tumor sample (PMID: 23715574), and in one of two cell lines, increased cell proliferation and cell viability compared to wild-type Braf (PMID: 29533785). |
Associated Drug Resistance | |
Category Variants Paths |
BRAF mutant BRAF act mut BRAF L597R BRAF mutant BRAF L597X BRAF L597R |
Transcript | NM_004333.6 |
gDNA | chr7:g.140753345A>C |
cDNA | c.1790T>G |
Protein | p.L597R |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_001378474.1 | chr7:g.140753345A>C | c.1790T>G | p.L597R | RefSeq | GRCh38/hg38 |
NM_004333.6 | chr7:g.140753345A>C | c.1790T>G | p.L597R | RefSeq | GRCh38/hg38 |
NM_001378468.1 | chr7:g.140753345A>C | c.1790T>G | p.L597R | RefSeq | GRCh38/hg38 |
XM_005250045 | chr7:g.140753345A>C | c.1790T>G | p.L597R | RefSeq | GRCh38/hg38 |
NM_001378472.1 | chr7:g.140749333_140749334delTTinsAG | c.1789_1790delTTinsAG | p.L597R | RefSeq | GRCh38/hg38 |
NM_004333.5 | chr7:g.140753345A>C | c.1790T>G | p.L597R | RefSeq | GRCh38/hg38 |
NM_004333 | chr7:g.140753345A>C | c.1790T>G | p.L597R | RefSeq | GRCh38/hg38 |
NM_001378473.1 | chr7:g.140749333_140749334delTTinsAG | c.1789_1790delTTinsAG | p.L597R | RefSeq | GRCh38/hg38 |
NM_001354609.1 | chr7:g.140753345A>C | c.1790T>G | p.L597R | RefSeq | GRCh38/hg38 |
NM_001354609.2 | chr7:g.140753345A>C | c.1790T>G | p.L597R | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
BRAF L597R | Advanced Solid Tumor | sensitive | Trametinib | Preclinical | Actionable | Preclinical studies demonstrated the MEK inhibitor, Mekinist (trametinib) caused decreased activation of MEK and ERK in cells expressing BRAF L597R (PMID: 22798288). | 22798288 |
BRAF L597R | melanoma | predicted - sensitive | Dabrafenib | Preclinical - Patient cell culture | Actionable | In a preclinical study, Tafinlar (dabrafenib) treatment inhibited Erk activation and reduced viability of patient-derived melanoma cells harboring BRAF L597R in culture (PMID: 23715574). | 23715574 |
BRAF L597R | melanoma | predicted - sensitive | Vemurafenib | Case Reports/Case Series | Actionable | In a clinical case study, Zelboraf (vemurafenib) treatment inhibited growth of skin and lung nodules by 30% and resulted in a duration of response of over 4 months in a melanoma patient harboring BRAF L597R, and inhibited Erk activation and reduced viability of melanoma cells derived from the patient in culture (PMID: 23715574). | 23715574 |
BRAF L597R | Advanced Solid Tumor | sensitive | Vemurafenib | Preclinical | Actionable | In a preclinical study, treatment of cells expressing BRAF L597R with the BRAF inhibitor, Zelboraf (vemurafenib), decreased activation of MEK and ERK (PMID: 22798288). | 22798288 |
BRAF L597R | melanoma | predicted - sensitive | Sorafenib | Preclinical - Patient cell culture | Actionable | In a preclinical study, Nexavar (sorafenib) treatment inhibited viability of patient-derived melanoma cells harboring BRAF L597R in culture (PMID: 23715574). | 23715574 |
BRAF L597R | prostate cancer | sensitive | PLX8394 | Preclinical - Cell culture | Actionable | In a preclinical study, PLX8394 treatment inhibited Erk signaling and reduced proliferation of prostate cancer cells harboring BRAF L597R in culture (PMID: 30559419). | 30559419 |
BRAF L597R | lung adenocarcinoma | predicted - sensitive | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with lung adenocarcinoma harboring BRAF L597R demonstrated clinical improvement and a tumor response at 13 weeks with resolution of hepatic metastasis and mediastinal lymphadenopathy when treated with the combination of Tafinlar (dabrafenib) and Mekinist (trametinib), and at the 12 month follow up remained on treatment, showing no disease progression (PMID: 32540409). | 32540409 |
BRAF L597R | colorectal cancer | not predictive | Fluorouracil + Irinotecan + Leucovorin + Panitumumab | Case Reports/Case Series | Actionable | In a clinical study, the combination of Vectibix (panitumumab) with FOLFIRI as a second-line therapy resulted in stable disease with a PFS of 16.5 months in a patient with metastatic colorectal cancer harboring BRAF L597R (PMID: 31515458). | 31515458 |
BRAF L597R | prostate cancer | predicted - sensitive | PF-07799933 | Preclinical - Biochemical | Actionable | In a preclinical study, PF-07799933 inhibited Erk phosphorylation in prostate cancer cells harboring BRAF L597R in culture (PMID: 38691346). | 38691346 |