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BRAF L485_P490delinsY - Gene Variant Detail

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Gene BRAF
Variant L485_P490delinsY
Impact List indel
Protein Effect gain of function
Gene Variant Descriptions BRAF L485_P490delinsY results in a deletion of six amino acids in the protein kinase domain of the Braf protein from amino acids 485 to 490, combined with the insertion of a tyrosine (Y) at the same site (UniProt.org). L485_P490delinsY results in increased Mek/Erk phosphorylation, is transforming, and is associated with resistance to select RAF inhibitors in culture (PMID: 37656784).
Associated Drug Resistance Y
Category Variants Paths

BRAF mutant BRAF act mut BRAF L485_P490delinsY

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Transcript NM_004333.6
gDNA chr7:g.140778038_140778055delinsATA
cDNA c.1453_1470delinsTAT
Protein p.L485_P490delinsY
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
NM_004333 chr7:g.140778038_140778055delinsATA c.1453_1470delinsTAT p.L485_P490delinsY RefSeq GRCh38/hg38
NM_001378468.1 chr7:g.140778038_140778055delinsATA c.1453_1470delinsTAT p.L485_P490delinsY RefSeq GRCh38/hg38
NM_001378474.1 chr7:g.140778038_140778055delinsATA c.1453_1470delinsTAT p.L485_P490delinsY RefSeq GRCh38/hg38
NM_004333.6 chr7:g.140778038_140778055delinsATA c.1453_1470delinsTAT p.L485_P490delinsY RefSeq GRCh38/hg38
XM_047420769.1 chr7:g.140778038_140778055delinsATA c.1453_1470delinsTAT p.L485_P490delinsY RefSeq GRCh38/hg38
NM_004333.5 chr7:g.140778038_140778055delinsATA c.1453_1470delinsTAT p.L485_P490delinsY RefSeq GRCh38/hg38
XM_005250045 chr7:g.140778038_140778055delinsATA c.1453_1470delinsTAT p.L485_P490delinsY RefSeq GRCh38/hg38
NM_001354609.2 chr7:g.140778038_140778055delinsATA c.1453_1470delinsTAT p.L485_P490delinsY RefSeq GRCh38/hg38
NM_001354609.1 chr7:g.140778038_140778055delinsATA c.1453_1470delinsTAT p.L485_P490delinsY RefSeq GRCh38/hg38

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
BRAF L485_P490delinsY lung non-small cell carcinoma sensitive LY3009120 Preclinical Actionable In a preclinical study, a non-small cell lung carcinoma cell line harboring BRAF L485_P490delinsY was sensitive to LY3009120 in both culture and xenograft models, resulting in significant tumor regression and inhibition of MEK and ERK phosphorylation (PMID: 26732095). 26732095
BRAF L485_P490delinsY lung non-small cell carcinoma sensitive Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) inhibited growth of a non-small cell lung carcinoma cell line harboring BRAF L485_P490delinsY in culture (PMID: 26732095). 26732095
BRAF L485_P490delinsY lung non-small cell carcinoma sensitive Trametinib Preclinical - Cell culture Actionable In a preclinical study, Mekinist (trametinib) inhibited MAPK signaling and colony formation in a non-small cell lung cancer cell line harboring BRAF L485_P490delinsY in culture (PMID: 37656784). 37656784
BRAF L485_P490delinsY lung non-small cell carcinoma resistant Dabrafenib Preclinical Actionable In a preclinical study, a non-small cell lung carcinoma cell line harboring BRAF L485_P490delinsY was resistant to Tafinlar (dabrafenib) (PMID: 26732095). 26732095
BRAF L485_P490delinsY Advanced Solid Tumor predicted - sensitive Trametinib Preclinical - Biochemical Actionable In a preclinical study, Mekinist (trametinib) inhibited Mek and Erk phosphorylation in cells expressing BRAF L485_P490delinsY in culture (PMID: 37656784). 37656784
BRAF L485_P490delinsY 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 L485_P490delinsY in culture (PMID: 37656784). 37656784
BRAF L485_P490delinsY Advanced Solid Tumor predicted - resistant Encorafenib Preclinical - Biochemical Actionable In a preclinical study, Braftovi (encorafenib) did not inhibit Mek and Erk phosphorylation in cells expressing BRAF L485_P490delinsY in culture (PMID: 37656784). 37656784
BRAF L485_P490delinsY Advanced Solid Tumor predicted - resistant Dabrafenib Preclinical - Biochemical Actionable In a preclinical study, Tafinlar (dabrafenib) did not inhibit Mek and Erk phosphorylation in cells expressing BRAF L485_P490delinsY in culture (PMID: 37656784). 37656784
BRAF L485_P490delinsY 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 L485_P490delinsY in culture (PMID: 37656784). 37656784
BRAF L485_P490delinsY lung non-small cell carcinoma sensitive LXH 254 Preclinical - Cell culture Actionable In a preclinical study, LXH 254 inhibited MAPK signaling and colony formation in a non-small cell lung cancer cell line harboring BRAF L485_P490delinsY in culture (PMID: 37656784). 37656784
BRAF L485_P490delinsY lung non-small cell carcinoma decreased response Encorafenib Preclinical - Cell culture Actionable In a preclinical study, a non-small cell lung cancer cell line harboring BRAF L485_P490delinsY was less sensitive to Braftovi (encorafenib) treatment compared to type II RAF inhibitors in culture (PMID: 37656784). 37656784
BRAF L485_P490delinsY lung non-small cell carcinoma sensitive Sorafenib Preclinical - Cell culture Actionable In a preclinical study, Nexavar (sorafenib) inhibited colony formation in a non-small cell lung cancer cell line harboring BRAF L485_P490delinsY in culture (PMID: 37656784). 37656784
BRAF L485_P490delinsY lung non-small cell carcinoma predicted - sensitive Ulixertinib Preclinical - Biochemical Actionable In a preclinical study, Ulixertinib (BVD-523) inhibited metabolic activity in a non-small cell lung cancer cell line harboring BRAF L485_P490delinsY in culture (PMID: 37656784). 37656784
BRAF L485_P490delinsY lung non-small cell 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 non-small cell lung cancer cell line harboring BRAF L485_P490delinsY in culture (PMID: 37656784). 37656784
BRAF L485_P490delinsY lung non-small cell 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 non-small cell lung cancer cell line harboring BRAF L485_P490delinsY in culture (PMID: 37656784). 37656784