Gene Variant Detail

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Gene KIT
Variant A829P
Impact List missense
Protein Effect gain of function
Gene Variant Descriptions KIT A829P lies within the protein kinase domain of the Kit protein (UniProt.org). A829P results in constitutive phosphorylation of Kit, activation of Akt and Erk signaling, and confers acquired resistance to imatinib in culture (PMID: 23582185).
Associated Drug Resistance Y

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Transcript NM_000222.2
gDNA chr4:g.54736498G>C
cDNA c.2485G>C
Protein p.A829P
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
XM_005265741.1 chr4:g.54736498G>C c.2485G>C p.A829P RefSeq GRCh38/hg38
NM_000222.2 chr4:g.54736498G>C c.2485G>C p.A829P RefSeq GRCh38/hg38
NM_000222 chr4:g.54736498G>C c.2485G>C p.A829P RefSeq GRCh38/hg38
XM_005265741 chr4:g.54736498G>C c.2485G>C p.A829P RefSeq GRCh38/hg38

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
KIT A829P melanoma resistant Sunitinib Preclinical Actionable In a preclinical study, melanoma cells expressing KIT A829P demonstrated resistance to treatment with Sutent (sunitinib) (PMID: 23582185, PMID: 25594040). 23582185 25594040
KIT A829P Advanced Solid Tumor sensitive Ponatinib Preclinical Actionable In a preclinical study, cells expressing KIT A829P demonstrated sensitivity to Iclusig (ponatinib) in an in vitro kinase assay (PMID: 25239608). 25239608
KIT A829P 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 A829P in culture, however, with decreased potency compared to its potency against other KIT variants (PMID: 31205508). 31205508
KIT A829P melanoma resistant Imatinib Preclinical Actionable In a preclinical study, melanoma cells expressing KIT A829P demonstrated resistance to treatment with Gleevec (imatinib mesylate) (PMID: 23582185, PMID: 25594040). 23582185 25594040
KIT A829P melanoma sensitive Nilotinib Preclinical Actionable In a preclinical study, Tasigna (nilotinib) demonstrated efficacy by inhibiting proliferation of cultured melanoma cells expressing KIT A829P (PMID: 23582185, PMID: 25594040). 23582185 25594040
KIT A829P melanoma sensitive Dasatinib Preclinical Actionable In a preclinical study, Sprycel (dasatinib) demonstrated efficacy by inhibiting proliferation of cultured melanoma cells expressing KIT A829P (PMID: 23582185, PMID: 25594040). 23582185 25594040
KIT V560_Y578del KIT A829P gastrointestinal stromal tumor decreased response Sunitinib Preclinical Actionable In a preclinical study, a patient derived GIST cell line co-harboring KIT V560_Y578del and KIT A829P demonstrated a decreased response to treatment with Sutent (sunitinib) (PMID: 25239608). 25239608
KIT W557_K558del KIT A829P Advanced Solid Tumor sensitive Ponatinib Preclinical Actionable In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT A829P were sensitive to Iclusig (ponatinib) in an in vitro kinase assay (PMID: 25239608). 25239608
KIT W557_K558del KIT A829P Advanced Solid Tumor sensitive Avapritinib Preclinical - Cell culture Actionable In a preclinical study, Ayvakit (avapritinib) treatment resulted in decreased viability of transformed cells expressing KIT W557_K558del and KIT A829P in culture, but was less effective compared to other treatments (PMID: 32350132). 32350132
KIT W557_K558del KIT A829P Advanced Solid Tumor conflicting Regorafenib Preclinical Actionable In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT A829P were resistant to Stivarga (regorafenib) in an in vitro kinase assay (PMID: 25239608). 25239608
KIT W557_K558del KIT A829P Advanced Solid Tumor conflicting Regorafenib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT W557_K558del and KIT A829P were sensitive to treatment with Stivarga (regorafenib), but demonstrated a decreased response compared to cells expressing KIT W557_K558del alone in culture (PMID: 32350132). 32350132
KIT W557_K558del KIT A829P Advanced Solid Tumor sensitive AZD3229 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT W557_K558del and KIT A829P demonstrated sensitivity to AZD3229 in culture, resulting in reduced cell viability (PMID: 32350132). 32350132
KIT W557_K558del KIT A829P Advanced Solid Tumor resistant Imatinib Preclinical Actionable In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT A829P were resistant to Gleevec (imatinib) in an in vitro kinase assay (PMID: 25239608). 25239608
KIT W557_K558del KIT A829P Advanced Solid Tumor resistant Imatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT W557_K558del and KIT A829P demonstrated resistance to Gleevec (imatinib) in culture (PMID: 32350132). 32350132
KIT W557_K558del KIT A829P Advanced Solid Tumor resistant Sunitinib Preclinical Actionable In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT A829P were resistant to Sutent (sunitinb) in an in vitro kinase assay (PMID: 25239608). 25239608
KIT W557_K558del KIT A829P Advanced Solid Tumor resistant Sunitinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT W557_K558del and KIT A829P demonstrated resistance to Sutent (sunitinb) in culture (PMID: 32350132). 32350132
KIT W557_K558del KIT A829P Advanced Solid Tumor sensitive Ripretinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT W557_K558del and KIT A829P demonstrated sensitivity to Qinlock (ripretinib) in culture, resulting in reduced cell viability (PMID: 32350132). 32350132
KIT exon11 KIT A829P gastrointestinal stromal tumor sensitive Imatinib + MK2206 Preclinical - Cell culture Actionable In a preclinical study, the combination of Gleevec (imatinib) and MK2206 demonstrated synergy in inhibiting growth of a Gleevec (imatinib)-resistant gastrointestinal stromal tumor cell line harboring a KIT exon 11 mutation and KIT A829P in culture (PMID: 27370604). 27370604
KIT V559D KIT A829P Advanced Solid Tumor sensitive Flumatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing KIT A829P and KIT V559D were sensitive to Flumatinib in culture, demonstrating decreased cell proliferation and inhibition of Kit, Erk1/2, and Stat3 phosphorylation (PMID: 24205792). 24205792
KIT V559D KIT A829P Advanced Solid Tumor no benefit Sunitinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing KIT A829P and KIT V559D were insensitive to Sutent (sunitinib) in culture (PMID: 24205792). 24205792
KIT V559_G565del KIT V654A KIT A829P gastrointestinal stromal tumor predicted - sensitive Ripretinib Case Reports/Case Series Actionable In a Phase I trial, treatment with Qinlock (ripretinib) decreased circulating tumor DNA, resulted in stable disease lasting over 26 months in a patient with gastrointestinal stromal tumor harboring a primary KIT V559_G565del mutation and two acquired resistance mutations, KIT V654A and KIT A829P (PMID: 31085175; NCT02571036). 31085175
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
KIT act mut skin melanoma sensitive Imatinib Guideline Actionable Gleevec (imatinib) is included in guidelines as second-line therapy for metastatic or unresectable cutaneous melanoma patients with KIT activating mutations (NCCN.org). detail...
KIT act mut gastrointestinal stromal tumor not applicable N/A Guideline Diagnostic KIT activating mutations aid the diagnosis of gastrointestinal stromal tumor (NCCN.org). detail...
KIT act mut gastrointestinal stromal tumor sensitive Pexidartinib Preclinical - Cell line xenograft Actionable In a preclinical study, PLX3397 inhibited growth of gastrointestinal stromal tumor cell lines harboring KIT activating mutations in culture and in cell line xenograft models (PMID: 24583793). 24583793
KIT act mut gastrointestinal stromal tumor sensitive Cabozantinib Preclinical Actionable In a preclinical study, Cometriq (cabozantinib) decreased cell viability in imatinib-sensitive and resistant gastrointestinal stromal tumor (GIST) cell lines harboring KIT activating mutations in culture, and induced tumor regression in KIT-mutant GIST mouse models (PMID: 25836719). 25836719
KIT act mut Advanced Solid Tumor sensitive PLX9486 Preclinical Actionable In a preclinical study, PLX9486 inhibited KIT mutations, including exon 17 mutations, and demonstrated in vivo and in vitro activity against tumors harboring KIT exon 17 mutations (Cancer Res February 1, 2016 76; IA32). detail...
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 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 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 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 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
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 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...