Gene Variant Detail

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Gene KIT
Variant D677N
Impact List missense
Protein Effect unknown
Gene Variant Descriptions KIT D677N lies within the protein kinase domain of the Kit protein (UniProt.org). D677N is associated with drug resistance when in the context of an activating KIT mutation (PMID: 31270078), but has not been biochemically characterized and therefore, its effect on Kit protein function is unknown (PubMed, Apr 2022).
Associated Drug Resistance Y

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Transcript NM_000222.2
gDNA chr4:g.54729373G>A
cDNA c.2029G>A
Protein p.D677N
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
NM_000222.2 chr4:g.54729373G>A c.2029G>A p.D677N RefSeq GRCh38/hg38
XM_017008178.1 chr4:g.54729373G>A c.2029G>A p.D677N RefSeq GRCh38/hg38
NM_000222 chr4:g.54729373G>A c.2029G>A p.D677N RefSeq GRCh38/hg38
XM_017008178 chr4:g.54729373G>A c.2029G>A p.D677N RefSeq GRCh38/hg38

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  • Use quotes to match a longer phrase which contains spaces "mtor c1483f"

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
KIT D677N KIT D816V Advanced Solid Tumor predicted - sensitive Avapritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing KIT D816V and KIT D677N demonstrated some sensitivity to treatment with Ayvakit (avapritinib) in culture (PMID: 31270078). 31270078
KIT D677N KIT D816V Advanced Solid Tumor resistant Midostaurin Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing KIT D816V and KIT D677N demonstrated resistance to treatment with Rydapt (midostaurin) in culture compared to cells expressing KIT D816V alone (PMID: 31270078). 31270078
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
KIT mutant melanoma sensitive Nilotinib Phase II Actionable In a Phase II trial, Tasigna (nilotinib) treatment resulted in complete response in 4% (1/25), durable partial response in 16% (4/25), and stable disease in 56% (14/25) of melanoma patients harboring KIT mutations (PMID: 28843487; NCT01168050). 28843487
KIT mutant melanoma sensitive Nilotinib Phase II Actionable In a Phase II trial, Tasigna (nilotinib) treatment in patients with melanoma harboring KIT mutations resulted in an overall response rate of 26.2% (11/42), which included 11 patients with a partial response, a median duration of response of 7.1 months, and an overall survival of 18 months (PMID: 28327988; NCT01028222). 28327988
KIT mutant gastrointestinal stromal tumor not applicable N/A Clinical Study Diagnostic KIT mutations are used in the diagnosis of gastrointestinal stromal tumors (PMID: 25193432, PMID: 26276366, PMID: 25729899). 25193432 26276366 25729899
KIT mutant gastrointestinal stromal tumor predicted - sensitive Ripretinib Phase I Actionable In a Phase I trial, Qinlock (ripretinib) was well tolerated, resulted in an objective response in 11.3% (16/142, 16 partial responses) and stable disease in 61.3% (87/142) of patients with advanced gastrointestinal stromal tumor harboring KIT (exon 11, n=103; exon 9, n=26; other, n=6) or PDGFRA mutations (n=7), with a median progression-free survival of 5.6 months (PMID: 32804590; NCT02571036). 32804590
KIT mutant gastrointestinal stromal tumor predicted - sensitive Ripretinib Phase I Actionable In a Phase I trial, Qinlock (ripretinib) demonstrated preliminary safety and efficacy in patients with advanced solid tumors, including KIT-mutant gastrointestinal stromal tumor (GIST), with 1 patient harboring KIT exon 11 and 17 mutations demonstrating a partial response, and 7/7 KIT-mutant GIST patients demonstrating a partial metabolic response (EORTC-NCI-AACR 2016, Abs 7LBA). detail...
KIT mutant melanoma predicted - sensitive Ripretinib Phase I Actionable In a Phase I trial, Qinlock (ripretinib) treatment demonstrated manageable safety and preliminary efficacy in patients with KIT-mutated melanoma, and led to an objective response rate of 23% (6/26, 1 complete and 5 partial responses), a median progression-free survival of 7.3 months, and a median duration of response of 7.4 months (Annals of Oncology 32 (2021): S896-S897; NCT02571036). detail...
KIT mutant gastrointestinal stromal tumor predicted - sensitive Avapritinib Phase I Actionable In a Phase I (NAVIGATOR) trial, Ayvakit (avapritinib) treatment resulted in an objective response rate of 13% (7/52, 7 partial responses) and a disease control rate of 63% (33/52) in patients with KIT-mutant gastrointestinal stromal tumor (The CTOS 2018 Annual Meeting, Nov 14-17, Rome Italy, Paper 012 3027631; NCT02508532). detail...
KIT mutant gastrointestinal stromal tumor sensitive Imatinib + Infigratinib Preclinical - Pdx Actionable In a preclinical study, Truseltiq (infigratinib) and Gleevec (imatinib) combination treatment demonstrated enhanced antitumor activity in patient derived xenograft models of gastrointestinal stromal tumor harboring KIT mutations (PMID: 25673643). 25673643
Molecular Profile Protein Effect Treatment Approaches
KIT D677N unknown
KIT D677N KIT D816V