Gene Variant Detail

Gene KIT
Variant L576P
Impact List missense
Protein Effect gain of function
Gene Variant Descriptions KIT L576P lies within the juxtamembrane domain 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

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Transcript NM_000222
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_000222 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

Filtering

  • Case insensitive filtering will display rows where any text in any cell matches the filter term
  • Simple literal full or partial string matches
  • Separate multiple filter terms with a spaces, order doesn't matter (a b c and c b a are equivalent )
  • Filtering will only apply to rows that are already loaded on the page, filtering has no impact on query parameters
  • Use quotes to match a longer phrase which contains spaces "mtor c1483f"

Sorting

  • Generally, the default sort order for tables is set to be first column ascending, however, specific tables may set a different default sort order.
  • Click on any column header arrows to sort by that column
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Molecular Profile Protein Effect Treatment Approaches
KIT L576P gain of function KIT Inhibitor
KIT L576P KIT W557R
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
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 sensitive Dasatinib Clinical Study Actionable In two clinical case studies, patients with Gleevec (imatinib)-melanoma that harboring KIT L576P demonstrated initial clinical benefit following treatment with Sprycel (dasatinib), however progressed after 3-4 months of treatment (PMID: 19671763). 19671763
KIT L576P melanoma sensitive Bevacizumab + Sorafenib Clinical Study Actionable In a clinical case study, 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 no benefit Imatinib Clinical Study Actionable In a clinical case report, Gleevec (imatinib mesylate) treatment resulted in initial tumor reduction followed by disease progression in a patient with metastasized labial melanoma harboring KIT L576P (PMID: 20372153). 20372153
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
KIT L576P melanoma sensitive Nilotinib Phase II 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 KIT W557R melanoma sensitive Nilotinib Phase II Actionable In a Phase II trial, Tasigna (nilotinib) resulted in an overall response rate of 26.2% (11/41) including a melanoma patient co-harboring KIT L576P and KIT W557R demonstrating a partial response and a progression free survival of 5.3 months and overall survival of 14.7 months when treated with Tasigna (nilotinib) (PMID: 28327988). 28327988