Gene Variant Detail

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Gene KIT
Variant V654A
Impact List missense
Protein Effect unknown
Gene Variant Descriptions KIT V654A lies within the protein kinase domain (exon 13) of the Kit protein (UniProt.org). V654A has been described as a secondary drug resistance mutation (PMID: 17363509, PMID: 16751810), but has conflicting functional data, as in some studies, results in increased proliferation in cultured cells and in murine cells (corresponding to V653A), leads to increased proliferation and elevated Stat activation in the context of KIT V559del (corresponding to V558del in mouse) in culture (PMID: 33024275), is constitutively phosphorylated in culture (PMID: 27440273), but in another study is not transforming and does not result in constitutive activation (PMID: 17363509), and therefore, its effect on Kit protein function is unknown.
Associated Drug Resistance Y
Category Variants Paths

KIT mutant KIT exon13 KIT V654X KIT V654A

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Transcript NM_000222.2
gDNA chr4:g.54728092T>C
cDNA c.1961T>C
Protein p.V654A
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
XM_017008178.1 chr4:g.54728092T>C c.1961T>C p.V654A RefSeq GRCh38/hg38
XM_017008178 chr4:g.54728092T>C c.1961T>C p.V654A RefSeq GRCh38/hg38
NM_000222.2 chr4:g.54728092T>C c.1961T>C p.V654A RefSeq GRCh38/hg38
NM_000222 chr4:g.54728092T>C c.1961T>C p.V654A RefSeq GRCh38/hg38

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  • Simple literal full or partial string matches
  • Separate multiple filter terms with a spaces, order doesn't matter (a b c and c b a are equivalent )
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  • Use quotes to match a longer phrase which contains spaces "mtor c1483f"

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
KIT V654A Advanced Solid Tumor resistant Imatinib Preclinical Actionable In a preclinical study, cells expressing KIT V654A demonstrated resistance to Gleevec (imatinib) in culture (PMID: 16751810). 16751810
KIT V654A Advanced Solid Tumor sensitive Ponatinib Preclinical Actionable In a preclinical study, cells expressing KIT V654A demonstrated some sensitivity to Iclusig (ponatinib) in an in vitro kinase assay (PMID: 25239608). 25239608
KIT V654A Advanced Solid Tumor sensitive Axitinib Preclinical - Cell line xenograft Actionable In a preclinical study, Inlyta (axitinib) inhibited KIT phosphorylation and proliferation of transformed cells expressing KIT V654A in culture, and inhibited tumor growth in xenograft models (PMID: 31205508). 31205508
KIT V654A Advanced Solid Tumor sensitive Sunitinib Preclinical - Cell culture Actionable In a preclinical study, Sutent (sunitinib) inhibited proliferation of transformed cells expressing KIT V654A in culture (PMID: 31205508). 31205508
KIT V654A Advanced Solid Tumor sensitive Sunitinib Preclinical - Cell culture Actionable In a preclinical study, Sutent (sunitinib) inhibited proliferation of transformed cells expressing KIT V654A in culture (PMID: 35194937). 35194937
KIT V654A gastrointestinal stromal tumor predicted - resistant Avapritinib Phase I Actionable In a Phase I trial, patients with gastrointestinal stromal tumors harboring either KIT V654A or KIT T670I demonstrated decreased overall response rate (0%, 0/25 vs. 26%, 22/84) and increased progressive disease rate (72% vs 23%) compared to those without either KIT mutation when treated with Ayvakit (avapritinib) (PMID: 31270078; NCT02508532). 31270078
KIT V654A Advanced Solid Tumor sensitive Nintedanib Preclinical - Cell culture Actionable In a preclinical study, Ofev (nintedanib) inhibited proliferation of transformed cells expressing KIT V654A in culture (PMID: 35194937). 35194937