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Gene | BRAF |
Variant | R506_K507insLLR |
Impact List | insertion |
Protein Effect | gain of function |
Gene Variant Descriptions | BRAF R506_K507insLLR results in the insertion of three amino acids in the protein kinase domain of the Braf protein between amino acids 506 and 507 (UniProt.org). R506_K507insLLR results in impaired Braf homodimerization and heterodimerization, confers resistance to RAF inhibitors, and leads to increased phosphorylation of Erk1/2 and downstream signaling, and foci formation in cultured cells (PMID: 34108213). |
Associated Drug Resistance | Y |
Category Variants Paths |
BRAF mutant BRAF act mut BRAF R506_K507insLLR |
Transcript | NM_004333.6 |
gDNA | chr7:g.140777090_140777091insAAGAAGCCT |
cDNA | c.1518_1519insCTTCTTAGG |
Protein | p.R506_K507insLLR |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
XM_047420769.1 | chr7:g.140777090_140777091insAAGAAGCCT | c.1518_1519insCTTCTTAGG | p.R506_K507insLLR | RefSeq | GRCh38/hg38 |
NM_004333.5 | chr7:g.140777090_140777091insAAGAAGCCT | c.1518_1519insCTTCTTAGG | p.R506_K507insLLR | RefSeq | GRCh38/hg38 |
NM_001378468.1 | chr7:g.140777090_140777091insAAGAAGCCT | c.1518_1519insCTTCTTAGG | p.R506_K507insLLR | RefSeq | GRCh38/hg38 |
NM_001354609.2 | chr7:g.140777090_140777091insAAGAAGCCT | c.1518_1519insCTTCTTAGG | p.R506_K507insLLR | RefSeq | GRCh38/hg38 |
NM_001354609.1 | chr7:g.140777090_140777091insAAGAAGCCT | c.1518_1519insCTTCTTAGG | p.R506_K507insLLR | RefSeq | GRCh38/hg38 |
NM_004333.6 | chr7:g.140777090_140777091insAAGAAGCCT | c.1518_1519insCTTCTTAGG | p.R506_K507insLLR | RefSeq | GRCh38/hg38 |
NM_001378474.1 | chr7:g.140777090_140777091insAAGAAGCCT | c.1518_1519insCTTCTTAGG | p.R506_K507insLLR | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
BRAF R506_K507insLLR | 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 R506_K507insLLR and inhibited tumor growth in cell line xenograft models (PMID: 34108213). | 34108213 |
BRAF R506_K507insLLR | Advanced Solid Tumor | resistant | Dabrafenib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, cells expressing BRAF R506_K507insLLR were resistant to treatment with Tafinlar (dabrafenib) in culture and cell line xenograft models (PMID: 34108213). | 34108213 |
BRAF R506_K507insLLR | Advanced Solid Tumor | resistant | Vemurafenib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, cells expressing BRAF R506_K507insLLR were resistant to treatment with Zelboraf (vemurafenib) in culture and cell line xenograft models (PMID: 34108213). | 34108213 |
BRAF R506_K507insLLR | Advanced Solid Tumor | predicted - sensitive | Binimetinib | Preclinical - Biochemical | Actionable | In a preclinical study, Mektovi (binimetinib) treatment inhibited Erk signaling in cells expressing BRAF R506_K507insLLR in culture (PMID: 34108213). | 34108213 |
BRAF R506_K507insLLR | Advanced Solid Tumor | predicted - sensitive | Selumetinib | Preclinical - Biochemical | Actionable | In a preclinical study,Koselugo (selumetinib) treatment inhibited Erk signaling in cells expressing BRAF R506_K507insLLR in culture (PMID: 34108213). | 34108213 |
BRAF R506_K507insLLR | Advanced Solid Tumor | predicted - resistant | Sorafenib | Preclinical - Biochemical | Actionable | In a preclinical study, cells expressing BRAF R506_K507insLLR were resistant to treatment with Nexavar (sorafenib) in culture (PMID: 34108213). | 34108213 |
BRAF R506_K507insLLR | Advanced Solid Tumor | predicted - sensitive | Cobimetinib | Preclinical - Biochemical | Actionable | In a preclinical study, Cotellic (cobimetinib) treatment inhibited Erk signaling in cells expressing BRAF R506_K507insLLR in culture (PMID: 34108213). | 34108213 |
BRAF R506_K507insLLR | Advanced Solid Tumor | resistant | PLX8394 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, cells expressing BRAF R506_K507insLLR were resistant to treatment with PLX8394 in culture and cell line xenograft models (PMID: 34108213). | 34108213 |
BRAF R506_K507insLLR | Advanced Solid Tumor | predicted - resistant | LY3009120 | Preclinical - Biochemical | Actionable | In a preclinical study, cells expressing BRAF R506_K507insLLR were resistant to treatment with LY3009120 in culture (PMID: 34108213). | 34108213 |