KIT L576P

CI-VAR-00002363Explore in graph →NP_000213.1:p.Leu576ProNM_000222.2:c.1727T>CClinVar 375919 CIViC 72 rs121913513

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 Tumor3
KIT L576P	Imatinib	Predictive	D	Supports Sensitivity Response	—	submitted	EID2479 Molecular models predict that deletion of a portion of the juxtamembrane domain relieves steric hindrance and results in higher binding affinity for imatinib. PMID 21364689 · Pierotti et al., 2011 · Open in CIViC	civic
KIT L576P	Sunitinib	Predictive	C	Supports Resistance	2	accepted	EID4136 Patient 29 from a larger cohort of genotyped patients (n= 78) with imatinib resistant or intolerant gastrointestinal stromal tumors (GISTs) harbored a primary (pre-imatinib treatment) KIT L576P mutati… (full text at CIViC) PMID 18955458 · Heinrich et al., 2008 · Open in CIViC	civic
KIT L576P

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
375919	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts	2	Gastrointestinal stromal tumor; Hereditary cancer-predisposing syndrome; Autosomal dominant KIT-related disorders	germline/somatic	4	Apr 29, 2025	clinvar

Lung Non-Small Cell Carcinoma1
KIT L576P	Dasatinib + Imatinib + NilotinibSubstitutes	Predictive	D	Supports Sensitivity Response	3	accepted	EID303 Ba/F3 cells harboring the KIT L576P mutation are sensitive to nilotinib, imatinib and lower concentrations of dasatinib. PMID 17372901 · Antonescu et al., 2007 · Open in CIViC	civic

Malignant Neoplasm1
KIT L576P	Dasatinib + ImatinibSubstitutes	Predictive	D	Supports Sensitivity Response	2	accepted	EID4141 In an in vitro study, COS-7 cells expressing KIT L576P activating mutation demonstrated sensitivity to imatinib and dasatinib treatments. Sensitivity was determined by assessing reduced mutant KIT aut… (full text at CIViC) PMID 25317746 · Vita et al., 2014 · Open in CIViC	civic

Melanoma2
KIT L576P	Dasatinib	Predictive	D	Supports Sensitivity Response	3	accepted	EID42 The melanoma cell line WM3211, which harbors the L576P mutation, is sensitive to dasatinib. Molecular modeling indicated the L576P mutation alters the conformation of KIT but did not alter the binding… (full text at CIViC) PMID 19671763 · Woodman et al., 2009 · Open in CIViC	civic
KIT L576P	Imatinib + Nilotinib + SorafenibSubstitutes	Predictive	D	Supports Resistance	3	accepted	EID34 The melanoma cell line WM3211 (derived from an acral lentiginous melanoma), which harbors the L576P mutation, is not sensitive to imatinib, nilotinib, and sorafenib. Molecular modeling indicated the L… (full text at CIViC) PMID 19671763 · Woodman et al., 2009 · Open in CIViC	civic