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Gene | BRAF |
Variant | G596R |
Impact List | missense |
Protein Effect | loss of function - predicted |
Gene Variant Descriptions | BRAF G596R lies within the protein kinase domain of the Braf protein (UniProt.org). G596R results in activation of Erk in the presence of CRAF (PMID: 19735675, PMID: 28783719, PMID: 18697864) and in another study demonstrates similar cell proliferation and viability levels to wild-type Braf (PMID: 29533785), but results in impaired Braf kinase activity and decreased Mek and Erk phosphorylation, including in the presence of BRAF V600E, is not transforming in culture, and does not promote tumor formation in mouse models (PMID: 19735675, PMID: 28783719), and therefore, is predicted to lead to a loss of Braf protein function. |
Associated Drug Resistance | |
Category Variants Paths |
BRAF mutant BRAF G596X BRAF G596R BRAF mutant BRAF inact mut BRAF G596R |
Transcript | NM_004333.6 |
gDNA | chr7:g.140753349C>G |
cDNA | c.1786G>C |
Protein | p.G596R |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_004333 | chr7:g.140753349C>G | c.1786G>C | p.G596R | RefSeq | GRCh38/hg38 |
XM_005250045 | chr7:g.140753349C>G | c.1786G>C | p.G596R | RefSeq | GRCh38/hg38 |
NM_001378468.1 | chr7:g.140753349C>G | c.1786G>C | p.G596R | RefSeq | GRCh38/hg38 |
NM_001354609.2 | chr7:g.140753349C>G | c.1786G>C | p.G596R | RefSeq | GRCh38/hg38 |
NM_001354609.1 | chr7:g.140753349C>G | c.1786G>C | p.G596R | RefSeq | GRCh38/hg38 |
NM_001378474.1 | chr7:g.140753349C>G | c.1786G>C | p.G596R | RefSeq | GRCh38/hg38 |
NM_004333.6 | chr7:g.140753349C>G | c.1786G>C | p.G596R | RefSeq | GRCh38/hg38 |
NM_004333.5 | chr7:g.140753349C>G | c.1786G>C | p.G596R | RefSeq | GRCh38/hg38 |
NM_001378467.1 | chr7:g.140753358C>G | c.1786G>C | p.G596R | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
BRAF G596R PIK3CA E545K | colorectal cancer | sensitive | Neratinib | Preclinical | Actionable | In a preclinical study, Nerlynx (neratinib) inhibited growth of colorectal cancer cells harboring both BRAF G596R and PIK3CA E545K in culture (PMID: 26243863). | 26243863 |
BRAF G596R PIK3CA E545K | colorectal cancer | resistant | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, colorectal cancer cells harboring BRAF G596R and PIK3CA E545K did not demonstrate sensitivity to Zelboraf (vemurafenib) treatment in culture (PMID: 22180495). | 22180495 |