KIT K642E

CI-VAR-00002153Explore in graph →NP_000213.1:p.Lys642GluNM_000222.2:c.1924A>GClinVar 13866 CIViC 978 rs121913512

Curated evidence

Evidence by cancer (7 items)

Grouped by cancer context first, then therapy. The same variant can be sensitizing in one cancer and irrelevant in another — contexts are never merged. 50 items per page; a cancer group may continue on the next page.

civicCuratedShowing 1–7 of 7 evidence items across 4 cancer contexts on this page · levels, directions and significance as curated at the source; each row links to its CIViC record.

Molecular profile	Therapy	Type	Level	Direction · significance	Rating (1–5)	Status	Evidence	Source
Gastrointestinal Stromal Tumor4
KIT K642E	Ponatinib + SunitinibSubstitutes	Predictive	D	Supports Sensitivity Response	3	accepted	EID7397 The GIST882 patient derived cell line expressing KIT K642E mutation demonstrated sensitivity to ponatinib (IC50: 31nmol/L) and sunitinib (IC50: 54nmol/L) treatments. In comparison, the insensitve KIT-… (full text at CIViC) PMID 25239608 · Garner et al., 2014 · Open in CIViC	civic
KIT K642E	Regorafenib Anhydrous	Predictive	D	Supports Sensitivity Response	—	submitted	EID4146 In an in vitro study, a GIST 882 cell line expressing KIT K642E mutation demonstrated increased sensitivity to regorafenib treatment (IC50: 45 nM vs. 560-3269nM) compared to HepG2, SW620, Colo-205 or … (full text at CIViC) PMID 21170960 ·

ClinVar

Clinical significance (1)

ClinVar interpretations are shown as structured records — significance, review status, star rating, conditions — never flattened into one word.

clinvarCurated1 interpretation · review status and star rating as assigned by ClinVar.

Variation	Clinical significance	Review status	Stars	Conditions	Origin	Submitters	Last evaluated	Source
13866	Pathogenic	criteria provided, multiple submitters, no conflicts	2	Gastrointestinal stromal tumor, familial; Gastrointestinal stromal tumor; Germinoma	germline/somatic	5	Feb 04, 2025	clinvar

Malignant Neoplasm1
KIT K642E	Imatinib	Predictive	D	Does Not Support Resistance	2	accepted	EID2472 In an in vitro study of imatinib sensitivity, KIT K642E was cloned into a plasmid by site-directed mutagenesis of KIT WT cDNA. Chinese hamster ovary cells were transiently transfected with the plasmid… (full text at CIViC) PMID 14645423 · Heinrich et al., 2003 · Open in CIViC	civic

Melanoma1
KIT K642E	Dasatinib	Predictive	C	Supports Sensitivity Response	—	accepted	EID4147 In a phase 2 clinical trial of 39 stage 3/4 chemotherapy-naive unresectable melanoma patients, a subungual melanoma patient harboring the KIT K642E mutation was reported to have a partial response to … (full text at CIViC) PMID 21523734 · Kluger et al., 2011 · Open in CIViC	civic

Mucosal Melanoma1
KIT K642E	Imatinib	Predictive	C	Supports Sensitivity Response	2	accepted	EID2889 A 69 y.o. woman presented with metastatic mucosal melanoma of the anus. KIT was amplified in the tumor and harbored the K642E mutation. Post surgery with extensive margins, she was given a dose of ant… (full text at CIViC) PMID 18510589 · Lutzky et al., 2008 · Open in CIViC	civic