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Gene | KIT |
Variant | V560D |
Impact List | missense |
Protein Effect | gain of function |
Gene Variant Descriptions | KIT V560D lies within the juxtamembrane domain (exon 11) of the Kit protein (PMID: 19164557). V560D confers a gain of function to Kit, as indicated by constitutive phosphorylation of Kit in cell culture (PMID: 16954519, PMID: 20633291, PMID: 27440273) despite reduced expression, enhanced degradation, and cellular mislocalization (PMID: 27440273). |
Associated Drug Resistance | |
Category Variants Paths |
KIT mutant KIT act mut KIT V560D KIT mutant KIT exon11 KIT V560D |
Transcript | NM_000222.3 |
gDNA | chr4:g.54727447T>A |
cDNA | c.1679T>A |
Protein | p.V560D |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
XM_017008178 | chr4:g.54727447T>A | c.1679T>A | p.V560D | RefSeq | GRCh38/hg38 |
NM_000222 | chr4:g.54727447T>A | c.1679T>A | p.V560D | RefSeq | GRCh38/hg38 |
NM_001385290.1 | chr4:g.54727444T>A | c.1679T>A | p.V560D | RefSeq | GRCh38/hg38 |
XM_005265740.1 | chr4:g.54727444T>A | c.1679T>A | p.V560D | RefSeq | GRCh38/hg38 |
NM_000222.2 | chr4:g.54727447T>A | c.1679T>A | p.V560D | RefSeq | GRCh38/hg38 |
XM_005265740 | chr4:g.54727444T>A | c.1679T>A | p.V560D | RefSeq | GRCh38/hg38 |
XM_005265741.1 | chr4:g.54727444T>A | c.1679T>A | p.V560D | RefSeq | GRCh38/hg38 |
XM_017008178.1 | chr4:g.54727447T>A | c.1679T>A | p.V560D | RefSeq | GRCh38/hg38 |
NM_000222.3 | chr4:g.54727447T>A | c.1679T>A | p.V560D | RefSeq | GRCh38/hg38 |
NM_001385284.1 | chr4:g.54727444T>A | c.1679T>A | p.V560D | RefSeq | GRCh38/hg38 |
XM_005265741 | chr4:g.54727444T>A | c.1679T>A | p.V560D | RefSeq | GRCh38/hg38 |
NM_001385285.1 | chr4:g.54727447T>A | c.1679T>A | p.V560D | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
KIT V560D | Advanced Solid Tumor | sensitive | Dasatinib | Preclinical | Actionable | In a preclinical study, transformed cells expressing KIT V560D were sensitive to Sprycel (dasatinib) in culture (PMID: 16397263). | 16397263 |
KIT V560D | Advanced Solid Tumor | sensitive | Imatinib | Preclinical | Actionable | In a preclinical study, transformed cells expressing KIT V560D demonstrated sensitivity to treatment with Gleevec (imatinib) in culture, resulting in reduced cell viability (PMID: 25239608). | 25239608 |
KIT V560D | Advanced Solid Tumor | sensitive | Motesanib Diphosphate | Preclinical - Cell culture | Actionable | In a preclinical study, Motesanib (AMG 706) inhibited KIT phosphorylation and growth of cells expressing KIT V560D in culture (PMID: 20633291). | 20633291 |
KIT V560D | melanoma | predicted - sensitive | Nilotinib | Case Reports/Case Series | Actionable | In a Phase II trial, Tasigna (nilotinib) resulted in an overall response rate of 26.2% (11/41) including a melanoma patient harboring KIT V560D demonstrating a partial response and progression free survival of 8.6 months and overall survival of 23.5 months (PMID: 28327988). | 28327988 |
KIT V560D | Advanced Solid Tumor | sensitive | Ponatinib | Preclinical | Actionable | In a preclinical study, transformed cells expressing KIT V560D demonstrated sensitivity to treatment with Iclusig (ponatinib) in culture, resulting in reduced cell viability (PMID: 25239608). | 25239608 |
KIT V560D | Advanced Solid Tumor | sensitive | Regorafenib | Preclinical | Actionable | In a preclinical study, transformed cells expressing KIT V560D demonstrated sensitivity to treatment with Stivarga (regorafineb) in culture, resulting in reduced cell viability (PMID: 25239608). | 25239608 |
KIT V560D | Advanced Solid Tumor | sensitive | Sorafenib | Preclinical | Actionable | In a preclinical study, transformed cells expressing KIT V560D were sensitive to Nexavar (sorafenib) in culture (PMID: 22665524). | 22665524 |
KIT V560D | Advanced Solid Tumor | sensitive | Sunitinib | Preclinical | Actionable | In a preclinical study, transformed cells expressing KIT V560D demonstrated sensitivity to treatment with Sutent (sunitinib) in culture, resulting in reduced cell viability (PMID: 25239608). | 25239608 |
KIT V560D | gastrointestinal stromal tumor | predicted - sensitive | Binimetinib + Imatinib | Case Reports/Case Series | Actionable | In a Phase II trial, Gleevec (imatinib) and Mektovi (binimetinib) combination treatment had manageable toxicity and resulted in a 95% pathological response and 6% RECIST response in a patient with gastrointestinal stromal tumor of the stomach harboring KIT V560D (PMID: 35041493; NCT01991379). | 35041493 |
KIT V560D | gastrointestinal stromal tumor | predicted - sensitive | Avapritinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT V560D were sensitive to treatment with Ayvakit (avapritinib) in culture, demonstrating decreased cell growth (PMID: 31270078). | 31270078 |
KIT V560D | Advanced Solid Tumor | sensitive | Avapritinib | Preclinical - Cell culture | Actionable | In a preclinical study, Ayvakit (avapritinib) treatment resulted in decreased cell viability in transformed cells expressing KIT V560D in culture, but was less potent compared to treatment with AZD3229 (PMID: 32350132). | 32350132 |
KIT V560D | Advanced Solid Tumor | sensitive | Ripretinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT V560D demonstrated sensitivity to Qinlock (ripretinib) in culture, resulting in reduced cell viability (PMID: 32350132). | 32350132 |
KIT V560D | Advanced Solid Tumor | sensitive | AZD3229 | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT V560D demonstrated sensitivity to AZD3229 in culture, resulting in reduced cell viability (PMID: 32350132). | 32350132 |