Annotation Detail

Information
Associated Genes
KIT
Associated Variants
KIT p.Ser629Asn (p.S629N) ( ENST00000288135.6, ENST00000412167.7, ENST00000686011.1, ENST00000687109.1, ENST00000687246.1, ENST00000687295.1, ENST00000689832.1, ENST00000689994.1, ENST00000690543.1, ENST00000692783.1 )
KIT p.Ser629Asn (p.S629N) ( ENST00000288135.6, ENST00000412167.7, ENST00000686011.1, ENST00000687109.1, ENST00000687246.1, ENST00000687295.1, ENST00000689832.1, ENST00000689994.1, ENST00000690543.1, ENST00000692783.1 )
Associated Disease
melanoma
Source Database
CIViC Evidence
Description
A melanoma patient harboring the KIT S628N activating mutation underwent second-line imatinib therapy following lung metastatic progression that appeared after an eighth cycle of chemotherapy. The S628N mutation was not present in the blood, which confirmed that it was a somatic mutation. After 3 months of imatinib treatment (300 mg/d for first three weeks, then 400 mg/d), the patient exhibited disease progression and increased tumor size, and after an additional three months of imatinib treatment (400 mg/d), the patient developed multiple supratentorial brain metastases in addition to increased lung metastases and died 5 days later. The authors reported preclinical data which indicated variant sensitivity to imatinib. although this outcome did not coroberate the preclinical result, the authors still concluded the variant may be sensitive.
Variant Origin
somatic
Variant Origin
Somatic
Evidence URL
https://civic.genome.wustl.edu/links/evidence_items/7463
Gene URL
https://civic.genome.wustl.edu/links/genes/29
Variant URL
https://civic.genome.wustl.edu/links/variants/1659
Rating
3
Evidence Type
Predictive
Disease
Melanoma
Evidence Direction
Does Not Support
Drug
Imatinib
Evidence Level
C
Clinical Significance
Sensitivity/Response
Pubmed
25317746
Drugs
Drug NameSensitivitySupported
ImatinibSensitivityfalse