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Gene | BRAF |
Variant | V504_R506dup |
Impact List | duplication |
Protein Effect | gain of function |
Gene Variant Descriptions | BRAF V504_R506dup (also referred to as R506_K507insVLR) indicates the insertion of three amino acids, valine (V)-504 through arginine (R)-506, in the protein kinase domain of the Braf protein (UniProt.org). V504_R506dup confers a gain of function to the Braf protein as demonstrated by stabilization of Braf homodimers, increased downstream Erk phosphorylation in cultured cells (PMID: 23817572, PMID: 30575814), and association with increased Erk1/2 phosphorylation in human tumor samples (PMID: 29544532), and has been associated with resistance to select Raf and Mek inhibitors in cultured cells (PMID: 30575814). |
Associated Drug Resistance | Y |
Category Variants Paths |
BRAF mutant BRAF act mut BRAF V504_R506dup |
Transcript | NM_004333.6 |
gDNA | chr7:g.140777088_140777998 |
cDNA | c.1510_1518 |
Protein | p.V504_R506 |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_004333.6 | chr7:g.140777088_140777998 | c.1510_1518 | p.V504_R506 | RefSeq | GRCh38/hg38 |
NM_001354609.2 | chr7:g.140777088_140777998 | c.1510_1518 | p.V504_R506 | RefSeq | GRCh38/hg38 |
NM_004333 | chr7:g.140777090_140777091insAAGTACCCT | c.1518_1519insGTACTTAGG | p.V504_R506dupVLR | RefSeq | GRCh38/hg38 |
XM_047420769.1 | chr7:g.140777088_140777998 | c.1510_1518 | p.V504_R506 | RefSeq | GRCh38/hg38 |
XM_005250045 | chr7:g.140777090_140777091insAAGTACCCT | c.1518_1519insGTACTTAGG | p.V504_R506dupVLR | RefSeq | GRCh38/hg38 |
NM_004333.5 | chr7:g.140777088_140777998 | c.1510_1518 | p.V504_R506 | RefSeq | GRCh38/hg38 |
NM_001354609.1 | chr7:g.140777088_140777998 | c.1510_1518 | p.V504_R506 | RefSeq | GRCh38/hg38 |
NM_001378468.1 | chr7:g.140777088_140777998 | c.1510_1518 | p.V504_R506 | RefSeq | GRCh38/hg38 |
NM_001378474.1 | chr7:g.140777088_140777998 | c.1510_1518 | p.V504_R506 | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
BRAF V504_R506dup | Advanced Solid Tumor | sensitive | Trametinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Mekinist (trametinib) treatment resulted in decreased Erk signaling in cultured cells expressing BRAF V504_R506dup and inhibited tumor growth in cell line xenograft models (PMID: 34108213). | 34108213 |
BRAF V504_R506dup | Advanced Solid Tumor | sensitive | Trametinib | Preclinical - Biochemical | Actionable | In a preclinical study, Mekinist (trametinib) treatment resulted in decreased Erk1/2 phosphorylation in transformed cells expressing BRAF V504_R506dup in culture (PMID: 30575814). | 30575814 |
BRAF V504_R506dup | Advanced Solid Tumor | resistant | Dabrafenib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, cells expressing BRAF V504_R506dup were resistant to treatment with Tafinlar (dabrafenib) in culture and cell line xenograft models (PMID: 34108213). | 34108213 |
BRAF V504_R506dup | Advanced Solid Tumor | resistant | Vemurafenib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, cells expressing BRAF V504_R506dup were resistant to treatment with Zelboraf (vemurafenib) in culture and cell line xenograft models (PMID: 34108213). | 34108213 |
BRAF V504_R506dup | Advanced Solid Tumor | resistant | Vemurafenib | Preclinical - Biochemical | Actionable | In a preclinical study, transformed cells overexpressing BRAF V504_R506dup were resistant to Zelboraf (vemurafenib) in culture (PMID: 30575814). | 30575814 |
BRAF V504_R506dup | Advanced Solid Tumor | predicted - resistant | Sorafenib | Preclinical - Biochemical | Actionable | In a preclinical study, cells expressing BRAF V504_R506dup were resistant to treatment with Nexavar (sorafenib) in culture (PMID: 34108213). | 34108213 |
BRAF V504_R506dup | Advanced Solid Tumor | predicted - resistant | Sorafenib | Preclinical - Biochemical | Actionable | In a preclinical study, transformed cells overexpressing BRAF V504_R506dup were resistant to Nexavar (sorafenib) in culture (PMID: 30575814). | 30575814 |
BRAF V504_R506dup | Advanced Solid Tumor | resistant | PLX8394 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, cells expressing BRAF V504_R506dup were resistant to treatment with PLX8394 in culture and cell line xenograft models (PMID: 34108213). | 34108213 |
BRAF V504_R506dup | Advanced Solid Tumor | predicted - resistant | LY3009120 | Preclinical - Biochemical | Actionable | In a preclinical study, cells expressing BRAF V504_R506dup were resistant to treatment with LY3009120 in culture (PMID: 34108213). | 34108213 |