chr4:54728092:T>C Detail (hg38) (KIT)

Information

Genome

Assembly Position
hg19 chr4:55,594,258-55,594,258 View the variant detail on this assembly version.
hg38 chr4:54,728,092-54,728,092

HGVS

Type Transcript Protein
RefSeq NM_000222.2:c.1961T>C NP_000213.1:p.Val654Ala
NM_001093772.1:c.1952T>C NP_001087241.1:p.Val651Ala
Ensemble ENST00000288135.6:c.1961T>C ENST00000288135.6:p.Val654Ala
Summary

MGeND

Clinical significance
Variant entry
GWAS entry
Disease area statistics Show details

Frequency

[No Data.]

Prediction

ClinVar

Clinical Significance Uncertain significance
Review star
Show details
Links
Type Database ID Link
Gene MIM 164920 OMIM
HGNC 6342 HGNC
Ensembl ENSG00000157404 Ensembl
NCBI NCBI
Gene Cards Gene Cards
OncoKB OncoKB
Type Database ID Link
Variant TogoVar
COSMIC COSM12706 COSMIC
MONDO
Disease area statistics
[No Data.]
MGeND
[No Data.]
ClinVar
Clinical significance Last evaluated Review status Condition Origin Links
Pathogenic 2014-10-02 no assertion criteria provided melanoma somatic Detail
Uncertain significance 2023-08-04 criteria provided, single submitter gastrointestinal stromal tumor somatic germline Detail
CIViC
Disease Drug EL ET ED CS VO TR Pubmed Links
gastrointestinal stromal tumor Imatinib D Predictive Supports Resistance Somatic 3 16954519 Detail
gastrointestinal stromal tumor Sunitinib B Predictive Supports Sensitivity/Response Somatic 3 16638875 Detail
DisGeNET
Score Disease name Description Source Pubmed Links
0.760 Gastrointestinal Stromal Tumors The reported mechanism of imatinib resistance in GISTs involves missense mutatio... BeFree 15946589 Detail
0.760 Gastrointestinal Stromal Tumors We expressed c-KIT cDNA constructs encoding the V654A substitution alone and in ... BeFree 17363509 Detail
Annotation

Annotations

DescrptionSourceLinks
KIT V654A results in imatinib resistance in GIST patient-derived cell lines. CIViC Evidence Detail
In GIST tumor cells and patients harboring KIT V654A mutation, SU11248 is effective for those that a... CIViC Evidence Detail
NM_000222.3(KIT):c.1961T>C (p.Val654Ala) AND Melanoma ClinVar Detail
NM_000222.3(KIT):c.1961T>C (p.Val654Ala) AND Gastrointestinal stromal tumor ClinVar Detail
The reported mechanism of imatinib resistance in GISTs involves missense mutation in the kinase doma... DisGeNET Detail
We expressed c-KIT cDNA constructs encoding the V654A substitution alone and in combination with a t... DisGeNET Detail

Overlapped Transcript Coordinates

Gene Transcript ID Exon Number Chromosome Start Stop Type Amino Mutation Transcript Position Links

Overlapped Transcript

Gene Transcript ID Chromosome Start Stop Links
Gene
-
dbSNP
rs121913523 dbSNP
Genome
hg38
Position
chr4:54,728,092-54,728,092
Variant Type
snv
Reference Allele
T
Alternative Allele
C
Variant (CIViC) (CIViC Variant)
V654A
Transcript 1 (CIViC Variant)
ENST00000288135.5
Variant URL (CIViC Variant)
https://civic.genome.wustl.edu/links/variants/73
Summary (CIViC Variant)
KIT V654A is an exon 13 mutation that lies within the tyrosine kinase 1 domain of the protein. It has been shown to be an activating mutation by in vitro studies. This mutation is associated with imatinib resistance in melanoma patients. However, second generation TKI's such as sunitinib and midostaurin (PKC 412) have seen success in acheiving tumor response.
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