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Gene | BRAF |
Variant | V487_P492delinsA |
Impact List | indel |
Protein Effect | gain of function |
Gene Variant Descriptions | BRAF V487_P492delinsA results in a deletion of six amino acids in the protein kinase domain of the Braf protein from amino acids 487 to 492, combined with the insertion of an alanine (A) at the same site (UniProt.org). V487_P492delinsA results in increased Mek/Erk phosphorylation, cell proliferation and transformation (PMID: 26732095, PMID: 37656784), and confers resistance to select RAF inhibitors in culture (PMID: 37656784). |
Associated Drug Resistance | Y |
Category Variants Paths |
BRAF mutant BRAF act mut BRAF V487_P492delinsA |
Transcript | NM_004333.6 |
gDNA | chr7:g.140778034_140778048del15 |
cDNA | c.1460_1474del15 |
Protein | p.V487_P492delinsA |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_004333.6 | chr7:g.140778034_140778048del15 | c.1460_1474del15 | p.V487_P492delinsA | RefSeq | GRCh38/hg38 |
XM_047420769.1 | chr7:g.140778034_140778048del15 | c.1460_1474del15 | p.V487_P492delinsA | RefSeq | GRCh38/hg38 |
XM_005250045 | chr7:g.140778034_140778048del15 | c.1460_1474del15 | p.V487_P492delinsA | RefSeq | GRCh38/hg38 |
NM_004333.5 | chr7:g.140778034_140778048del15 | c.1460_1474del15 | p.V487_P492delinsA | RefSeq | GRCh38/hg38 |
NM_001354609.1 | chr7:g.140778034_140778048del15 | c.1460_1474del15 | p.V487_P492delinsA | RefSeq | GRCh38/hg38 |
NM_001354609.2 | chr7:g.140778034_140778048del15 | c.1460_1474del15 | p.V487_P492delinsA | RefSeq | GRCh38/hg38 |
NM_004333 | chr7:g.140778034_140778048del15 | c.1460_1474del15 | p.V487_P492delinsA | RefSeq | GRCh38/hg38 |
NM_001378474.1 | chr7:g.140778034_140778048del15 | c.1460_1474del15 | p.V487_P492delinsA | RefSeq | GRCh38/hg38 |
NM_001378468.1 | chr7:g.140778034_140778048del15 | c.1460_1474del15 | p.V487_P492delinsA | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
BRAF V487_P492delinsA | pancreatic cancer | sensitive | Trametinib | Preclinical | Actionable | In a preclinical study, a pancreatic cancer cell line harboring BRAF V487_P492delinsA was sensitive to Mekinist (trametinib) in culture, resulting in cell growth inhibition (PMID: 26732095). | 26732095 |
BRAF V487_P492delinsA | pancreatic carcinoma | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited MAPK signaling and colony formation in a pancreatic carcinoma cell line harboring BRAF V487_P492delinsA in culture (PMID: 37656784). | 37656784 |
BRAF V487_P492delinsA | Advanced Solid Tumor | predicted - sensitive | Trametinib | Preclinical - Biochemical | Actionable | In a preclinical study, Mekinist (trametinib) inhibited Mek and Erk phosphorylation in cells expressing BRAF V487_P492delinsA in culture (PMID: 37656784). | 37656784 |
BRAF V487_P492delinsA | pancreatic cancer | resistant | Dabrafenib | Preclinical | Actionable | In a preclinical study, a pancreatic cancer cell line harboring BRAF V487_P492delinsA was resistant to Tafinlar (dabrafenib) (PMID: 26732095). | 26732095 |
BRAF V487_P492delinsA | Advanced Solid Tumor | predicted - sensitive | Dabrafenib | Preclinical - Biochemical | Actionable | In a preclinical study, Tafinlar (dabrafenib) inhibited Mek and Erk phosphorylation in cells expressing BRAF V487_P492delinsA in culture (PMID: 37656784). | 37656784 |
BRAF V487_P492delinsA | pancreatic cancer | resistant | Vemurafenib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, a human pancreatic cancer cell line harboring BRAF V487_P492delinsA was resistant to treatment with Zelboraf (vemurafenib) in both culture and xenograft models (PMID: 26732095). | 26732095 |
BRAF V487_P492delinsA | pancreatic cancer | resistant | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, a pancreatic cancer cell line harboring BRAF V487_P492delinsA was resistant to Zelboraf (vemurafenib) in culture (PMID: 37164118). | 37164118 |
BRAF V487_P492delinsA | Advanced Solid Tumor | predicted - resistant | Vemurafenib | Preclinical - Biochemical | Actionable | In a preclinical study, Zelboraf (vemurafenib) did not inhibit Mek and Erk phosphorylation in cells expressing BRAF V487_P492delinsA in culture (PMID: 37656784). | 37656784 |
BRAF V487_P492delinsA | pancreatic carcinoma | decreased response | Encorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, a pancreatic carcinoma cell line harboring BRAF V487_P492delinsA was less sensitive to Braftovi (encorafenib) treatment compared to type II RAF inhibitors in culture (PMID: 37656784). | 37656784 |
BRAF V487_P492delinsA | pancreatic carcinoma | sensitive | Sorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Nexavar (sorafenib) inhibited colony formation in a pancreatic carcinoma cell line harboring BRAF V487_P492delinsA in culture (PMID: 37656784). | 37656784 |
BRAF V487_P492delinsA | pancreatic carcinoma | predicted - sensitive | Ulixertinib | Preclinical - Biochemical | Actionable | In a preclinical study, Ulixertinib (BVD-523) inhibited metabolic activity in a pancreatic carcinoma cell line harboring BRAF V487_P492delinsA in culture (PMID: 37656784). | 37656784 |
BRAF V487_P492delinsA | pancreatic carcinoma | predicted - sensitive | Sorafenib + Trametinib | Preclinical - Biochemical | Actionable | In a preclinical study, combination of Mekinist (trametinib) and Nexavar (sorafenib) resulted in enhanced inhibition of metabolic activity in a pancreatic carcinoma cell line harboring BRAF V487_P492delinsA in culture (PMID: 37656784). | 37656784 |
BRAF V487_P492delinsA | pancreatic cancer | sensitive | LY3009120 | Preclinical | Actionable | In a preclinical study, a pancreatic cancer cell line harboring BRAF V487_P492delinsA were sensitive to LY3009120 in culture and in xenograft models, resulting in inhibition of tumor growth and partial tumor regression (PMID: 26732095). | 26732095 |
BRAF V487_P492delinsA | pancreatic carcinoma | sensitive | LXH 254 | Preclinical - Cell culture | Actionable | In a preclinical study, LXH 254 inhibited MAPK signaling and colony formation in a pancreatic carcinoma cell line harboring BRAF V487_P492delinsA in culture (PMID: 37656784). | 37656784 |
BRAF V487_P492delinsA | Advanced Solid Tumor | predicted - sensitive | LXH 254 | Preclinical - Biochemical | Actionable | In a preclinical study, LXH 254 inhibited Mek and Erk phosphorylation in cells expressing BRAF V487_P492delinsA in culture (PMID: 37656784). | 37656784 |
BRAF V487_P492delinsA | pancreatic carcinoma | predicted - sensitive | LXH 254 + Trametinib | Preclinical - Biochemical | Actionable | In a preclinical study, combination of Mekinist (trametinib) and LXH 254 resulted in enhanced inhibition of metabolic activity in a pancreatic carcinoma cell line harboring BRAF V487_P492delinsA in culture (PMID: 37656784). | 37656784 |
BRAF V487_P492delinsA | pancreatic cancer | sensitive | IHMT-RAF-128 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, IHMT-RAF-128 inhibited proliferation in a pancreatic cancer cell line harboring BRAF V487_P492delinsA in culture and inhibited tumor growth in a cell line xenograft model (PMID: 37164118). | 37164118 |