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Gene | KIT |
Variant | V559A |
Impact List | missense |
Protein Effect | gain of function |
Gene Variant Descriptions | KIT V559A lies within the juxtamembrane domain (exon 11) of the Kit protein (PMID: 15837988). V559A results in constitutive phosphorylation of Kit and increased Mapk and Akt activation in patient samples and cultured cells (PMID: 15837988, PMID: 19047099). |
Associated Drug Resistance | |
Category Variants Paths |
KIT mutant KIT act mut KIT V559A KIT mutant KIT exon11 KIT V559X KIT V559A |
Transcript | NM_000222.3 |
gDNA | chr4:g.54727444T>C |
cDNA | c.1676T>C |
Protein | p.V559A |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_001385285.1 | chr4:g.54727444T>C | c.1676T>C | p.V559A | RefSeq | GRCh38/hg38 |
NM_000222.3 | chr4:g.54727444T>C | c.1676T>C | p.V559A | RefSeq | GRCh38/hg38 |
XM_017008178.1 | chr4:g.54727444T>C | c.1676T>C | p.V559A | RefSeq | GRCh38/hg38 |
XM_017008178 | chr4:g.54727444T>C | c.1676T>C | p.V559A | RefSeq | GRCh38/hg38 |
NM_000222 | chr4:g.54727444T>C | c.1676T>C | p.V559A | RefSeq | GRCh38/hg38 |
NM_000222.2 | chr4:g.54727444T>C | c.1676T>C | p.V559A | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
KIT V559A | 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 V559A in culture (PMID: 31205508). | 31205508 |
KIT V559A | melanoma | predicted - sensitive | Imatinib | Case Reports/Case Series | Actionable | In a clinical case study, Gleevec (imatinib) treatment in a patient with metastatic melanoma resulted in regression of the lung metastasis, which harbored KIT V559A; however, neither the primary tumor or lymph node metastasis responded, which had wild-type KIT (PMID: 19812602). | 19812602 |
KIT V559A | gastrointestinal stromal tumor | predicted - resistant | Imatinib | Case Reports/Case Series | Actionable | In a clinical study, KIT V559A was identified as a secondary mutation in a patient with gastrointestinal stromal tumor who developed resistance to Gleevec (imatinib) (PMID: 18488160). | 18488160 |
KIT V559A | 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 V559A demonstrating a partial response and progression-free survival of 19.4 months and overall survival of 32.9 months (PMID: 28327988). | 28327988 |