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Gene | BRAF |
Variant | V600R |
Impact List | missense |
Protein Effect | gain of function |
Gene Variant Descriptions | BRAF V600R (previously reported as V599) lies within the activation segment of the kinase domain of the Braf protein (PMID: 15035987). V600R confers a gain of function to the Braf protein as demonstrated by increased Braf kinase activity, downstream signaling, and the ability to transform cells in culture (PMID: 15035987, PMID: 29533785). |
Associated Drug Resistance | |
Category Variants Paths |
BRAF mutant BRAF act mut BRAF V600R BRAF mutant BRAF V600X BRAF V600R |
Transcript | NM_004333.6 |
gDNA | chr7:g.140753336_140753337delGTinsAG |
cDNA | c.1798_1799delGTinsAG |
Protein | p.V600R |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_004333.5 | chr7:g.140753336_140753337delGTinsAG | c.1798_1799delGTinsAG | p.V600R | RefSeq | GRCh38/hg38 |
NM_001354609.2 | chr7:g.140753336_140753337delGTinsAG | c.1798_1799delGTinsAG | p.V600R | RefSeq | GRCh38/hg38 |
NM_001378474.1 | chr7:g.140753336_140753337delGTinsAG | c.1798_1799delGTinsAG | p.V600R | RefSeq | GRCh38/hg38 |
NM_004333.6 | chr7:g.140753336_140753337delGTinsAG | c.1798_1799delGTinsAG | p.V600R | RefSeq | GRCh38/hg38 |
NM_004333 | chr7:g.140753336_140753337delACinsCT | c.1798_1799delGTinsAG | p.V600R | RefSeq | GRCh38/hg38 |
NM_001354609.1 | chr7:g.140753336_140753337delGTinsAG | c.1798_1799delGTinsAG | p.V600R | RefSeq | GRCh38/hg38 |
XM_005250045 | chr7:g.140753336_140753337delACinsCT | c.1798_1799delGTinsAG | p.V600R | RefSeq | GRCh38/hg38 |
NM_001378468.1 | chr7:g.140753336_140753337delGTinsAG | c.1798_1799delGTinsAG | p.V600R | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
BRAF V600R | melanoma | sensitive | AZ628 | Preclinical - Cell culture | Actionable | In a preclinical study, AZ628 inhibited proliferation of melanoma cell lines harboring BRAF V600R in culture (PMID: 27523909). | 27523909 |
BRAF V600R | melanoma | sensitive | TAK-632 | Preclinical - Cell culture | Actionable | In a preclinical study, TAK-632 inhibited proliferation of melanoma cell lines harboring BRAF V600R in culture (PMID: 27523909). | 27523909 |
BRAF V600R | melanoma | sensitive | PLX7904 | Preclinical - Cell culture | Actionable | In a preclinical study, PLX7904 inhibited proliferation of melanoma cells harboring BRAF V600R in culture (PMID: 27523909). | 27523909 |
BRAF V600R | melanoma | sensitive | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Zelboraf (vemurafenib) inhibited proliferation of melanoma cells harboring BRAF V600R in culture (PMID: 27523909). | 27523909 |
BRAF V600R | melanoma | sensitive | Dabrafenib | Case Reports/Case Series | Actionable | In a clinical case study, a melanoma patient harboring BRAF V600R treated with Tafinlar (dabrafenib) demonstrated a reduction in lesion size after 2.5 months and at 5 months, stable disease, however, after 7 months progression ensued (PMID: 27255157). | 27255157 |
BRAF V600R | melanoma | sensitive | Dabrafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Tafinlar (dabrafenib) inhibited proliferation of melanoma cells harboring BRAF V600R in culture (PMID: 27523909). | 27523909 |
BRAF V600R | melanoma | predicted - sensitive | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, the combination of Mekinist (trametinib) and Tafinlar (dabrafenib) resulted in a partial response in one of two patients with melanoma harboring BRAF V600R, with a progression-free survival of 52.2 months in the responding patient (PMID: 36039514). | 36039514 |