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Gene | KIT |
Variant | D820Y |
Impact List | missense |
Protein Effect | gain of function |
Gene Variant Descriptions | KIT D820Y lies within the protein kinase domain of the Kit protein (UniProt.org). D820Y results in constitutive phosphorylation of Kit and is transforming in cell culture (PMID: 19035443, PMID: 11984533), and has also been identified as a secondary drug mutation associated with imatinib resistance (PMID: 18488160). |
Associated Drug Resistance | Y |
Category Variants Paths |
KIT mutant KIT act mut KIT D820Y KIT mutant KIT exon17 KIT D820Y |
Transcript | NM_000222.3 |
gDNA | chr4:g.54733166G>T |
cDNA | c.2458G>T |
Protein | p.D820Y |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_000222.3 | chr4:g.54733166G>T | c.2458G>T | p.D820Y | RefSeq | GRCh38/hg38 |
XM_005265741 | chr4:g.54733166G>T | c.2458G>T | p.D820Y | RefSeq | GRCh38/hg38 |
XM_005265741.1 | chr4:g.54733166G>T | c.2458G>T | p.D820Y | RefSeq | GRCh38/hg38 |
NM_000222 | chr4:g.54733166G>T | c.2458G>T | p.D820Y | RefSeq | GRCh38/hg38 |
NM_000222.2 | chr4:g.54733166G>T | c.2458G>T | p.D820Y | RefSeq | GRCh38/hg38 |
NM_001385290.1 | chr4:g.54733166G>T | c.2458G>T | p.D820Y | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
KIT D820Y | melanoma | sensitive | Dasatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Sprycel (dasatinib) inhibited MNK pathway activation and proliferation of melanoma cell lines harboring KIT D820Y in culture (PMID: 29035277). | 29035277 |
KIT D820Y | melanoma | resistant | Imatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Gleevec (imatinib mesylate) failed to inhibit MNK pathway activation and proliferation of melanoma cell lines harboring KIT D820Y in culture (PMID: 29035277). | 29035277 |
KIT D820Y | Advanced Solid Tumor | sensitive | Nintedanib | Preclinical - Cell culture | Actionable | In a preclinical study, Ofev (nintedanib) inhibited proliferation of transformed cells expressing KIT D820Y in culture (PMID: 35194937). | 35194937 |
KIT D820Y | melanoma | predicted - sensitive | Sorafenib | Case Reports/Case Series | Actionable | In a clinical case study, Nexavar (sorafenib) treatment resulted in stable disease with 27% reduction in target lesions at 4 weeks in a patient with anal melanoma and pulmonary metastases harboring KIT D820Y (PMID: 20372153). | 20372153 |
KIT D820Y | melanoma | predicted - sensitive | Ripretinib | Case Reports/Case Series | Actionable | In a Phase I trial, Qinlock (ripretinib) treatment resulted in a complete response in a patient with metastatic melanoma harboring KIT D820Y (PMID: 35753087; NCT02571036). | 35753087 |
KIT D820Y | melanoma | sensitive | SEL201 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, SEL201 inhibited MNK pathway signaling and growth of melanoma cell lines harboring KIT D820Y in culture, and suppressed tumor metastasis in xenograft models (PMID: 29035277). | 29035277 |