BRAF G469V
Gene Variant Detail

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Gene BRAF
Variant G469V
Impact List missense
Protein Effect gain of function
Gene Variant Descriptions BRAF G469V is a hotspot mutation within the protein kinase domain of the Braf protein (UniProt.org). G469V results in increased Braf kinase activity and activation of downstream MEK and ERK in cell culture (PMID: 28947956, PMID: 26343582, PMID: 28783719), 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 G469V

BRAF mutant BRAF G469X BRAF G469V

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Transcript NM_004333.6
gDNA chr7:g.140781602C>A
cDNA c.1406G>T
Protein p.G469V
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
NM_001378467.1 chr7:g.140781611C>A c.1406G>T p.G469V RefSeq GRCh38/hg38
XM_047420769.1 chr7:g.140781602C>A c.1406G>T p.G469V RefSeq GRCh38/hg38
XM_005250045 chr7:g.140781602C>A c.1406G>T p.G469V RefSeq GRCh38/hg38
NM_001378470.1 chr7:g.140778000C>A c.1406G>T p.G469V RefSeq GRCh38/hg38
NM_004333.6 chr7:g.140781602C>A c.1406G>T p.G469V RefSeq GRCh38/hg38
NM_001378468.1 chr7:g.140781602C>A c.1406G>T p.G469V RefSeq GRCh38/hg38
NM_004333.5 chr7:g.140781602C>A c.1406G>T p.G469V RefSeq GRCh38/hg38
NM_001354609.2 chr7:g.140781602C>A c.1406G>T p.G469V RefSeq GRCh38/hg38
NM_004333 chr7:g.140781602C>A c.1406G>T p.G469V RefSeq GRCh38/hg38
NM_001354609.1 chr7:g.140781602C>A c.1406G>T p.G469V RefSeq GRCh38/hg38
NM_001378474.1 chr7:g.140781602C>A c.1406G>T p.G469V RefSeq GRCh38/hg38

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
BRAF G469V NRAS Q61K melanoma sensitive Encorafenib + Trametinib Preclinical - Cell culture Actionable In a preclinical study, the addition of Braftovi (encorafenib) to treatment with Mekinist (trametinib) resulted in increased growth inhibition in a melanoma cell line harboring BRAF G469V and NRAS Q61K in culture (PMID: 29903896). 29903896
BRAF G469V NRAS Q61K melanoma sensitive Binimetinib + Encorafenib Preclinical - Cell culture Actionable In a preclinical study, the addition of Braftovi (encorafenib) to treatment with Mektovi (binimetinib) resulted in increased growth inhibition in a melanoma cell line harboring BRAF G469V and NRAS Q61K in culture (PMID: 29903896). 29903896
BRAF G469V NRAS Q61K melanoma predicted - resistant Trametinib + Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, the addition of Zelboraf (vemurafenib) to treatment with Mekinist (trametinib) resulted in increased proliferation compared to Mekinist (trametinib) alone in a melanoma cell line harboring BRAF G469V and NRAS Q61K in culture (PMID: 29903896). 29903896
BRAF G469V NRAS Q61K melanoma sensitive LY3009120 Preclinical - Cell culture Actionable In a preclinical study, LY3009120 inhibited growth of a melanoma cell line harboring BRAF G469V and NRAS Q61K in culture (PMID: 29903896). 29903896
BRAF G469V NRAS Q61K melanoma no benefit Dabrafenib Preclinical - Cell culture Actionable In a preclinical study, Tafinlar (dabrafenib) treatment did not result in significant growth inhibition in a melanoma cell line harboring BRAF G469V and NRAS Q61K in culture (PMID: 29903896). 29903896