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Gene | KIT |
Variant | V559D |
Impact List | missense |
Protein Effect | gain of function |
Gene Variant Descriptions | KIT V559D lies within the juxtamembrane domain (exon 11) of the Kit protein (PMID: 9438854). V559D confers a gain of function on Kit, as indicated by constitutive Kit phosphorylation, and is transforming in cell culture (PMID: 9438854, PMID: 21689725). |
Associated Drug Resistance | |
Category Variants Paths |
KIT mutant KIT act mut KIT V559D KIT mutant KIT exon11 KIT V559X KIT V559D |
Transcript | NM_000222.3 |
gDNA | chr4:g.54727444T>A |
cDNA | c.1676T>A |
Protein | p.V559D |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
XM_017008178 | chr4:g.54727444T>A | c.1676T>A | p.V559D | RefSeq | GRCh38/hg38 |
XM_017008178.1 | chr4:g.54727444T>A | c.1676T>A | p.V559D | RefSeq | GRCh38/hg38 |
NM_001385285.1 | chr4:g.54727444T>A | c.1676T>A | p.V559D | RefSeq | GRCh38/hg38 |
NM_000222 | chr4:g.54727444T>A | c.1676T>A | p.V559D | RefSeq | GRCh38/hg38 |
NM_000222.2 | chr4:g.54727444T>A | c.1676T>A | p.V559D | RefSeq | GRCh38/hg38 |
NM_000222.3 | chr4:g.54727444T>A | c.1676T>A | p.V559D | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
KIT V559D | gastrointestinal stromal tumor | sensitive | Axitinib | Preclinical - Patient cell culture | Actionable | In a preclinical study, Inlyta (axitinib) inhibited proliferation of gastrointestinal stromal tumor patient-derived primary cells harboring KIT V559D in culture (PMID: 31205508). | 31205508 |
KIT V559D | Advanced Solid Tumor | sensitive | Axitinib | Preclinical - Cell culture | Actionable | In a preclinical study, Inlyta (axitinib) inhibited KIT phosphorylation and proliferation of transformed cells expressing KIT V559D in culture (PMID: 31205508). | 31205508 |
KIT V559D | Advanced Solid Tumor | sensitive | Dasatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Sprycel (dasatinib) decreased KIT signaling, and inhibited growth and induced apoptosis of transformed cells expressing KIT V559D in culture (PMID: 21689725). | 21689725 |
KIT V559D | Advanced Solid Tumor | sensitive | Imatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Gleevec (imatinib) decreased KIT signaling, and inhibited growth and induced apoptosis of transformed cells expressing KIT V559D in culture (PMID: 21689725). | 21689725 |
KIT V559D | Advanced Solid Tumor | sensitive | Imatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Gleevec (imatinib) inhibited proliferation of transformed cells expressing KIT V559D in culture (PMID: 35194937). | 35194937 |
KIT V559D | Advanced Solid Tumor | sensitive | Imatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT V559D were sensitive to Gleevec (imatinib), demonstrating decreased cell proliferation in culture and inhibition of Kit, Erk1/2, and Stat3 phosphorylation (PMID: 24205792). | 24205792 |
KIT V559D | 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 V559D demonstrating a partial response and progression free survival of 28.3 months and overall survival of 28.3 months (PMID: 28327988). | 28327988 |
KIT V559D | gastrointestinal stromal tumor | predicted - sensitive | Nintedanib | Preclinical - Patient cell culture | Actionable | In a preclinical study, Ofev (nintedanib) inhibited proliferation of patient-derived gastrointestinal stromal tumor cells harboring KIT V559D in culture (PMID: 35194937). | 35194937 |
KIT V559D | Advanced Solid Tumor | sensitive | Nintedanib | Preclinical - Cell culture | Actionable | In a preclinical study, Ofev (nintedanib) inhibited Kit autophosphorylation and proliferation of transformed cells expressing KIT V559D in culture (PMID: 35194937). | 35194937 |
KIT V559D | Advanced Solid Tumor | sensitive | Ponatinib | Preclinical | Actionable | In a preclinical study, cells expressing KIT V559D demonstrated sensitivity to Iclusig (ponatinib) in an in vitro kinase assay (PMID: 25239608). | 25239608 |
KIT V559D | Advanced Solid Tumor | sensitive | Sunitinib | Preclinical - Cell culture | Actionable | In a preclinical study, Sutent (sunitinib) inhibited proliferation of transformed cells expressing KIT V559D in culture (PMID: 35194937). | 35194937 |
KIT V559D | Advanced Solid Tumor | sensitive | Sunitinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT V559D were sensitive to Sutent (sunitinib), demonstrating decreased cell proliferation in culture and inhibition of Kit, Erk1/2, and Stat3 phosphorylation (PMID: 24205792). | 24205792 |
KIT V559D | Advanced Solid Tumor | sensitive | Flumatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT V559D were sensitive to Flumatinib, demonstrating decreased cell proliferation in culture and inhibition of Kit, Erk1/2, and Stat3 phosphorylation (PMID: 24205792). | 24205792 |