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Gene | KIT |
Variant | L576P |
Impact List | missense |
Protein Effect | gain of function |
Gene Variant Descriptions | KIT L576P lies within the juxtamembrane domain (exon 11) of the Kit protein (PMID: 17372901). L576P confers a gain of function to Kit, as indicated by constitutive phosphorylation of Kit, and is transforming in cell culture (PMID: 17372901). |
Associated Drug Resistance | |
Category Variants Paths |
KIT mutant KIT act mut KIT L576P KIT mutant KIT exon11 KIT L576P |
Transcript | NM_000222.3 |
gDNA | chr4:g.54727495T>C |
cDNA | c.1727T>C |
Protein | p.L576P |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_001385285.1 | chr4:g.54727495T>C | c.1727T>C | p.L576P | RefSeq | GRCh38/hg38 |
XM_017008178.1 | chr4:g.54727495T>C | c.1727T>C | p.L576P | RefSeq | GRCh38/hg38 |
NM_000222 | chr4:g.54727495T>C | c.1727T>C | p.L576P | RefSeq | GRCh38/hg38 |
NM_000222.2 | chr4:g.54727495T>C | c.1727T>C | p.L576P | RefSeq | GRCh38/hg38 |
XM_017008178 | chr4:g.54727495T>C | c.1727T>C | p.L576P | RefSeq | GRCh38/hg38 |
NM_000222.3 | chr4:g.54727495T>C | c.1727T>C | p.L576P | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
KIT L576P | Advanced Solid Tumor | sensitive | Axitinib | Preclinical - Cell culture | Actionable | In a preclinical study, Inlyta (axitinib) inhibited KIT phosphorylation and proliferation of transformed cells expressing KIT L576P in culture (PMID: 31205508). | 31205508 |
KIT L576P | melanoma | sensitive | Dasatinib | Case Reports/Case Series | Actionable | In a clinical study, two patients with melanoma harboring KIT L576P, one who had progressed on Gleevec (imatinib), demonstrated initial clinical benefit following treatment with Sprycel (dasatinib); however, one patient progressed after 3 months, and the other patient progressed after 4 months of treatment (PMID: 19671763). | 19671763 |
KIT L576P | melanoma | sensitive | Dasatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Sprycel (dasatinib) inhibited MNK pathway activation and proliferation of melanoma cell lines harboring KIT L576P in culture (PMID: 29035277). | 29035277 |
KIT L576P | melanoma | unknown | Imatinib | Case Reports/Case Series | Actionable | In a clinical case study, Gleevec (imatinib) treatment resulted in initial tumor reduction, but was followed by disease progression at all tumor sites in a patient with metastasized labial melanoma harboring KIT L576P (PMID: 20372153). | 20372153 |
KIT L576P | Advanced Solid Tumor | sensitive | Imatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Gleevec (imatinib) inhibited proliferation of transformed cells expressing KIT L576P in culture (PMID: 35194937). | 35194937 |
KIT L576P | melanoma | predicted - sensitive | Nilotinib | Case Reports/Case Series | Actionable | In a Phase II trial, Tasigna (nilotinib) resulted in an overall response rate of 26.2% (11/41) including three melanoma patients harboring KIT L576P demonstrating a partial response (PMID: 28327988). | 28327988 |
KIT L576P | Advanced Solid Tumor | sensitive | Nintedanib | Preclinical - Cell culture | Actionable | In a preclinical study, Ofev (nintedanib) inhibited Kit autophosphorylation and proliferation of transformed cells expressing KIT L576P in culture (PMID: 35194937). | 35194937 |
KIT L576P | Advanced Solid Tumor | sensitive | Sunitinib | Preclinical - Cell culture | Actionable | In a preclinical study, Sutent (sunitinib) inhibited proliferation of transformed cells expressing KIT L576P in culture (PMID: 35194937). | 35194937 |
KIT L576P | melanoma | predicted - sensitive | Ripretinib | Case Reports/Case Series | Actionable | In a Phase I trial, Qinlock (ripretinib) treatment resulted in a partial response in 3 of 4 patients with metastatic melanoma harboring KIT L576P (PMID: 35753087; NCT02571036). | 35753087 |
KIT L576P | melanoma | predicted - sensitive | Bevacizumab + Sorafenib | Case Reports/Case Series | Actionable | In a Phase I trial, a melanoma patient harboring KIT L576P demonstrated sensitivity to the combination treatment of Nexavar (sorafenib) and Avastin (bevacizumab), resulting in a partial response for 8 months (PMID: 25363205). | 25363205 |
KIT L576P | melanoma | sensitive | SEL201 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, SEL201 inhibited MNK pathway signaling and growth of melanoma cells harboring KIT L576P in culture, and suppressed tumor metastasis in xenograft models (PMID: 29035277). | 29035277 |