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Gene | KIT |
Variant | D816H |
Impact List | missense |
Protein Effect | gain of function |
Gene Variant Descriptions | KIT D816H lies within the tyrosine kinase domain region 2 (exon 17) of the Kit protein (PMID: 19164557). D816H results in increased kinase activity, constitutive Kit phosphorylation, activation of Stat3 signaling, and transformation of cultured cells (PMID: 10362788, PMID: 11494148), and confers resistance to some Kit inhibitors (PMID: 25239608). |
Associated Drug Resistance | Y |
Category Variants Paths |
KIT mutant KIT act mut KIT D816H KIT mutant KIT exon17 KIT D816X KIT D816H |
Transcript | NM_000222.3 |
gDNA | chr4:g.54733154G>C |
cDNA | c.2446G>C |
Protein | p.D816H |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
XM_005265741 | chr4:g.54733154G>C | c.2446G>C | p.D816H | RefSeq | GRCh38/hg38 |
XM_017008179 | chr4:g.54733166G>C | c.2446G>C | p.D816H | RefSeq | GRCh38/hg38 |
NM_000222.2 | chr4:g.54733154G>C | c.2446G>C | p.D816H | RefSeq | GRCh38/hg38 |
XM_005265741.1 | chr4:g.54733154G>C | c.2446G>C | p.D816H | RefSeq | GRCh38/hg38 |
XM_017008179.1 | chr4:g.54733166G>C | c.2446G>C | p.D816H | RefSeq | GRCh38/hg38 |
NM_001385290.1 | chr4:g.54733154G>C | c.2446G>C | p.D816H | RefSeq | GRCh38/hg38 |
NM_001093772 | chr4:g.54733166G>C | c.2446G>C | p.D816H | RefSeq | GRCh38/hg38 |
NM_001385292.1 | chr4:g.54733166G>C | c.2446G>C | p.D816H | RefSeq | GRCh38/hg38 |
NM_001093772.2 | chr4:g.54733166G>C | c.2446G>C | p.D816H | RefSeq | GRCh38/hg38 |
NM_000222 | chr4:g.54733154G>C | c.2446G>C | p.D816H | RefSeq | GRCh38/hg38 |
NM_000222.3 | chr4:g.54733154G>C | c.2446G>C | p.D816H | RefSeq | GRCh38/hg38 |
NM_001093772.1 | chr4:g.54733166G>C | c.2446G>C | p.D816H | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
KIT W557_K558del KIT D816H | Advanced Solid Tumor | sensitive | Ponatinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT D816H demonstrated sensitivity to treatment with Iclusig (ponatinib) in both culture and cell line xenograft models, resulting in reduced cell viability and tumor regression (PMID: 25239608). | 25239608 |
KIT W557_K558del KIT D816H | Advanced Solid Tumor | decreased response | Sunitinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT D816H demonstrated a decreased response to treatment with Sutent (sunitinib) in both culture and cell line xenograft models, resulting in only a slight decrease in tumor volume (PMID: 25239608). | 25239608 |
KIT W557_K558del KIT D816H | Advanced Solid Tumor | decreased response | Imatinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT D816H demonstrated a decreased response to treatment with Gleevec (imatinib) in both culture and xenograft models, resulting in only a slight decrease in tumor volume (PMID: 25239608). | 25239608 |
KIT W557_K558del KIT D816H | Advanced Solid Tumor | decreased response | Regorafenib | Preclinical | Actionable | In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT D816H demonstrated a decreased response to treatment with Stivarga (regorafenib) in culture (PMID: 25239608). | 25239608 |
KIT W557_K558del KIT D816H | Advanced Solid Tumor | sensitive | AZD3229 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, AZD3229 inhibited growth of cells in culture and tumor growth in a cell line xenograft model of transformed cells expressing KIT W557_K558del and KIT D816H (PMID: 32350132). | 32350132 |
KIT W557_K558del KIT D816H | Advanced Solid Tumor | sensitive | Avapritinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT W557_K558del and KIT D816H demonstrated sensitivity to Ayvakit (avapritinib) in culture, resulting in reduced cell viability (PMID: 32350132). | 32350132 |
KIT W557_K558del KIT D816H | Advanced Solid Tumor | sensitive | Ripretinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT W557_K558del and KIT D816H demonstrated sensitivity to Qinlock (ripretinib) in culture, resulting in reduced cell viability (PMID: 32350132). | 32350132 |
KIT W557_K558del KIT D816H | gastrointestinal stromal tumor | predicted - resistant | Imatinib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with gastrointestinal stromal tumor harboring KIT W557_K558del progressed after experiencing stable disease on treatment with Gleevec (imatinib), and was found to have acquired the secondary resistance mutation KIT D816H (PMID: 18294292). | 18294292 |
KIT V560D KIT D816H | Advanced Solid Tumor | sensitive | AZD3229 | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT V560D and KIT D816H demonstrated sensitivity to AZD3229 in culture, resulting in reduced cell viability (PMID: 32350132). | 32350132 |
KIT V560D KIT D816H | Advanced Solid Tumor | resistant | Imatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT V560D and KIT D816H demonstrated resistance to Gleevec (imatinib) in culture (PMID: 32350132). | 32350132 |
KIT V560D KIT D816H | Advanced Solid Tumor | resistant | Sunitinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT V560D and KIT D816H demonstrated resistance to Sutent (sunitinib) in culture (PMID: 32350132). | 32350132 |
KIT V560D KIT D816H | Advanced Solid Tumor | resistant | Regorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT V560D and KIT D816H demonstrated resistance to Stivarga (regorafenib) in culture (PMID: 32350132). | 32350132 |
KIT V560D KIT D816H | Advanced Solid Tumor | decreased response | Avapritinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT V560D and KIT D816H demonstrated a decreased response to treatment with Ayvakit (avapritinib) compared to cells expressing KIT V560D alone in culture (PMID: 32350132). | 32350132 |
KIT V560D KIT D816H | Advanced Solid Tumor | sensitive | Ripretinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT V560D and KIT D816H demonstrated sensitivity to Qinlock (ripretinib) in culture, resulting in reduced cell viability (PMID: 32350132). | 32350132 |
KIT A502_Y503dup KIT D816H | Advanced Solid Tumor | resistant | Imatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT A502_Y503dup and KIT D816H demonstrated resistance to Gleevec (imatinib) in culture (PMID: 32350132). | 32350132 |
KIT A502_Y503dup KIT D816H | Advanced Solid Tumor | resistant | Sunitinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT A502_Y503dup and KIT D816H demonstrated resistance to Sutent (sunitinib) in culture (PMID: 32350132). | 32350132 |
KIT A502_Y503dup KIT D816H | Advanced Solid Tumor | resistant | Regorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT A502_Y503dup and KIT D816H demonstrated resistance to Stivarga (regorafenib) in culture (PMID: 32350132). | 32350132 |
KIT A502_Y503dup KIT D816H | Advanced Solid Tumor | sensitive | AZD3229 | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT A502_Y503dup and KIT D816H demonstrated sensitivity to AZD3229 in culture, resulting in reduced cell viability (PMID: 32350132). | 32350132 |
KIT A502_Y503dup KIT D816H | Advanced Solid Tumor | sensitive | Avapritinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT A502_Y503dup and KIT D816H demonstrated increased sensitivity to treatment with Ayvakit (avapritinib) compared to cells expressing KIT A502_Y503dup alone in culture (PMID: 32350132). | 32350132 |
KIT A502_Y503dup KIT D816H | Advanced Solid Tumor | decreased response | Ripretinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT A502_Y503dup and KIT D816H demonstrated a decreased response to treatment with Qinlock (ripretinib) compared to cells expressing KIT A502_Y503dup alone in culture (PMID: 32350132). | 32350132 |
KIT exon 11 del KIT D816H | Advanced Solid Tumor | predicted - sensitive | THE-630 | Preclinical - Cell culture | Actionable | In a preclinical study, THE-630 treatment inhibited growth of cells co-expressing a KIT exon 11 deletion and KIT D816H in culture (Cancer Res 2021;81(13_Suppl):Abstract nr 1292). | detail... |
KIT W557_K558del KIT V654G KIT D816H | gastrointestinal stromal tumor | predicted - resistant | Ripretinib | Case Reports/Case Series | Actionable | In a retrospective study, a patient with a gastrointestinal stromal tumor harboring KIT W557_K558del and D816H progressed on sixth-line treatment with Qinlock (ripretinib) after 11.5 months and was found to have acquired KIT V654G in the metastatic lesion (PMID: 38408285). | 38408285 |