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Gene | BRAF |
Variant | F595L |
Impact List | missense |
Protein Effect | loss of function |
Gene Variant Descriptions | BRAF F595L lies within the protein kinase domain of the Braf protein (UniProt.org). F595L results in reduced Braf kinase activity (PMID: 28783719, PMID: 15035987), but works cooperatively with oncogenic Ras to activate MEK/ERK signaling, and is transforming in cell culture (PMID: 15035987, PMID: 26582644, PMID: 29533785). |
Associated Drug Resistance | |
Category Variants Paths |
BRAF mutant BRAF F595X BRAF F595L BRAF mutant BRAF inact mut BRAF F595L |
Transcript | NM_004333.6 |
gDNA | chr7:g.140753352A>G |
cDNA | c.1783T>C |
Protein | p.F595L |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
XM_005250045 | chr7:g.140753352A>G | c.1783T>C | p.F595L | RefSeq | GRCh38/hg38 |
NM_001378474.1 | chr7:g.140753352A>G | c.1783T>C | p.F595L | RefSeq | GRCh38/hg38 |
NM_001354609.2 | chr7:g.140753352A>G | c.1783T>C | p.F595L | RefSeq | GRCh38/hg38 |
NM_004333 | chr7:g.140753352A>G | c.1783T>C | p.F595L | RefSeq | GRCh38/hg38 |
NM_004333.5 | chr7:g.140753352A>G | c.1783T>C | p.F595L | RefSeq | GRCh38/hg38 |
NM_001378468.1 | chr7:g.140753352A>G | c.1783T>C | p.F595L | RefSeq | GRCh38/hg38 |
NM_004333.6 | chr7:g.140753352A>G | c.1783T>C | p.F595L | RefSeq | GRCh38/hg38 |
NM_001354609.1 | chr7:g.140753352A>G | c.1783T>C | p.F595L | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
BRAF F595L | Advanced Solid Tumor | resistant | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, treatment with Zelboraf (vemurafenib) did not reduce activation of Mek and Erk by BRAF F595L in transformed cells in culture (PMID: 26582644). | 26582644 |
BRAF F595L | colorectal cancer | not predictive | Fluorouracil + Leucovorin + Oxaliplatin + Panitumumab | Case Reports/Case Series | Actionable | In a clinical study, the combination of Vectibix (panitumumab) with FOLFOX as a first-line therapy resulted in a partial response with progression-free survival of 10.2 months in a patient with metastatic colorectal cancer harboring BRAF F595L (PMID: 31515458). | 31515458 |