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Gene | BRAF |
Variant | L485_P490del |
Impact List | deletion |
Protein Effect | gain of function |
Gene Variant Descriptions | BRAF L485_P490del results in the deletion of six amino acids within the alphaC-helix region in the protein kinase domain of the Braf protein (PMID: 26732095). L485_P490del confers a gain of function to the Braf protein as demonstrated by increased kinase activity, phosphorylation of downstream Mek and Erk, and transformation ability in cell culture (PMID: 26732095, PMID: 26996308), and is associated with resistance to select RAF inhibitor in cell culture (PMID: 26732095). |
Associated Drug Resistance | Y |
Category Variants Paths |
BRAF mutant BRAF act mut BRAF L485_P490del |
Transcript | NM_004333.6 |
gDNA | chr7:g.140778038_140778055del18 |
cDNA | c.1453_1470del18 |
Protein | p.L485_P490delLNVTAP |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_001378468.1 | chr7:g.140778038_140778055del18 | c.1453_1470del18 | p.L485_P490delLNVTAP | RefSeq | GRCh38/hg38 |
NM_001378472.1 | chr7:g.140776980_140776997del18 | c.1453_1470del18 | p.L485_H490delLYHHLH | RefSeq | GRCh38/hg38 |
NM_004333.5 | chr7:g.140778038_140778055del18 | c.1453_1470del18 | p.L485_P490delLNVTAP | RefSeq | GRCh38/hg38 |
NM_001378471.1 | chr7:g.140777025_140777042del18 | c.1453_1470del18 | p.K485_I490delKPQLAI | RefSeq | GRCh38/hg38 |
NM_001354609.2 | chr7:g.140778038_140778055del18 | c.1453_1470del18 | p.L485_P490delLNVTAP | RefSeq | GRCh38/hg38 |
XM_047420768.1 | chr7:g.140781660_140781677del18 | c.1455_1472del18 | p.D485_W490delDSSDDW | RefSeq | GRCh38/hg38 |
NM_004333.6 | chr7:g.140778038_140778055del18 | c.1453_1470del18 | p.L485_P490delLNVTAP | RefSeq | GRCh38/hg38 |
NM_004333 | chr7:g.140778038_140778055del18 | c.1453_1470del18 | p.L485_P490delLNVTAP | RefSeq | GRCh38/hg38 |
XM_047420769.1 | chr7:g.140778038_140778055del18 | c.1453_1470del18 | p.L485_P490delLNVTAP | RefSeq | GRCh38/hg38 |
XM_017012559.2 | chr7:g.140781660_140781677del18 | c.1455_1472del18 | p.D485_W490delDSSDDW | RefSeq | GRCh38/hg38 |
NM_001378470.1 | chr7:g.140777034_140777051del18 | c.1453_1470del18 | p.Y485_Q490delYSTKPQ | RefSeq | GRCh38/hg38 |
XM_047420770.1 | chr7:g.140734716_140734733del18 | c.1453_1470del18 | p.K485_A490delKIHRSA | RefSeq | GRCh38/hg38 |
NM_001354609.1 | chr7:g.140778038_140778055del18 | c.1453_1470del18 | p.L485_P490delLNVTAP | RefSeq | GRCh38/hg38 |
XM_047420766.1 | chr7:g.140778003_140778020del18 | c.1454_1471del18 | p.A485_V490delAFKNEV | RefSeq | GRCh38/hg38 |
NM_001374244.1 | chr7:g.140781660_140781677del18 | c.1455_1472del18 | p.D485_W490delDSSDDW | RefSeq | GRCh38/hg38 |
NM_001378469.1 | chr7:g.140777070_140777087del18 | c.1454_1471del18 | p.K485_N490delKTRHVN | RefSeq | GRCh38/hg38 |
NM_001378475.1 | chr7:g.140754194_140754211del18 | c.1454_1471del18 | p.I485_K490delIHRDLK | RefSeq | GRCh38/hg38 |
NM_001378467.1 | chr7:g.140778047_140778064del18 | c.1453_1470del18 | p.V485_V490delVKMLNV | RefSeq | GRCh38/hg38 |
XM_017012559.1 | chr7:g.140781660_140781677del18 | c.1455_1472del18 | p.D485_W490delDSSDDW | RefSeq | GRCh38/hg38 |
NM_001374258.1 | chr7:g.140781660_140781677del18 | c.1455_1472del18 | p.D485_W490delDSSDDW | RefSeq | GRCh38/hg38 |
XM_005250045 | chr7:g.140778038_140778055del18 | c.1453_1470del18 | p.L485_P490delLNVTAP | RefSeq | GRCh38/hg38 |
XM_017012558.1 | chr7:g.140781660_140781677del18 | c.1455_1472del18 | p.D485_W490delDSSDDW | RefSeq | GRCh38/hg38 |
NM_001378474.1 | chr7:g.140778038_140778055del18 | c.1453_1470del18 | p.L485_P490delLNVTAP | RefSeq | GRCh38/hg38 |
XM_047420767.1 | chr7:g.140781660_140781677del18 | c.1455_1472del18 | p.D485_W490delDSSDDW | RefSeq | GRCh38/hg38 |
XM_017012559 | chr7:g.140781660_140781677del18 | c.1455_1472del18 | p.D485_W490delDSSDDW | RefSeq | GRCh38/hg38 |
XM_017012558 | chr7:g.140781660_140781677del18 | c.1455_1472del18 | p.D485_W490delDSSDDW | RefSeq | GRCh38/hg38 |
NM_001378473.1 | chr7:g.140776980_140776997del18 | c.1453_1470del18 | p.L485_H490delLYHHLH | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
BRAF L485_P490del | Advanced Solid Tumor | predicted - resistant | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Zelboraf (vemurafenib) failed to inhibit phosphorylation of Mek and Erk in transformed cells expressing BRAF L485_P490del in culture (PMID: 26732095). | 26732095 |
BRAF L485_P490del | Advanced Solid Tumor | predicted - sensitive | LY3009120 | Preclinical - Cell culture | Actionable | In a preclinical study, LY3009120 inhibited phosphorylation of Mek and Erk in transformed cells expressing BRAF L485_P490del in culture (PMID: 26732095). | 26732095 |
BRAF L485_P490del | melanoma | predicted - sensitive | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with lymph node metastatic melanoma harboring BRAF L485_P490del and high CD274 (PD-L1) expression (TPS>=60%) experienced a partial response with regression of the target lesion after two cycles of second-line combination therapy with Tafinlar (dabrafenib) and Mekinist (trametinib), and at last follow up, demonstrated a sustained partial response and progression-free survival of at least 18 months (PMID: 36686670). | 36686670 |