KIT L576P: Gene Variant Detail - Cancer Knowledgebase (CKB)

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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

Variant Reference Transcript
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Transcript	NM_000222.3
gDNA	chr4:g.54727495T>C
cDNA	c.1727T>C
Protein	p.L576P
Source Database	RefSeq
Genome Build	GRCh38/hg38

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Showing 1 to 6 of 6 entries

Transcript	gDNA	cDNA	Protein	Source Database	Genome Build
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
NM_000222.3	chr4:g.54727495T>C	c.1727T>C	p.L576P	RefSeq	GRCh38/hg38
NM_001385285.1	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
XM_017008178.1	chr4:g.54727495T>C	c.1727T>C	p.L576P	RefSeq	GRCh38/hg38

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Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
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	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	predicted - sensitive	Imatinib	Case Reports/Case Series	Actionable	In a clinical case study, Gleevec (imatinib) treatment resulted in a 42% reduction of target lesions and an improvement of symptoms in a patient with metastasized labial melanoma harboring KIT L576P (PMID: 20372153).	20372153
KIT L576P	melanoma	predicted - sensitive	Imatinib	Case Reports/Case Series	Actionable	In a Phase II trial, Gleevec (imatinib) treatment resulted in a best overall response rate of 53.8% (7/13, all partial responses) in patients with mucosal, acral, or chronically sun-damaged skin melanoma harboring KIT activating mutations in exons 11 (n=9), 13 (n=3), and 17 (n=1), including 3 partial responses and 1 with stable disease in patients with melanoma harboring KIT L576P (PMID: 23775962; NCT00424515).	23775962
KIT L576P	melanoma	predicted - sensitive	Imatinib	Case Reports/Case Series	Actionable	In a Phase II trial, Gleevec (imatinib) treatment resulted in a durable objective response rate of 16% (4/25, 2 complete and 2 partial responses), a median time-to-progression of 12 weeks, and a median survival from treatment initiation of 46.3 weeks in patients with melanoma harboring KIT mutations, including 2 complete, 1 partial, 1 transient partial response, and 1 stable disease in patients harboring KIT L576P (n=7) (PMID: 21642685; NCT00470470).	21642685
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	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	acral lentiginous melanoma	predicted - sensitive	Nilotinib	Case Reports/Case Series	Actionable	In a Phase II trial, Tasigna (nilotinib) treatment resulted in an overall response rate of 16.7% (7/42, 1 complete and 6 partial responses) and a disease control rate of 57.1% in melanoma patients harboring KIT mutations (n=25), amplification (n=15), or both (n=2), including 1 complete and 2 partial responses in patients with acral melanoma harboring KIT L576P (n=4) (PMID: 26424760; NCT01099514).	26424760
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	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	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	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	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	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

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KIT L576PGene Variant Detail

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KIT L576P
Gene Variant Detail