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Gene | KIT |
Variant | W557_K558del |
Impact List | deletion |
Protein Effect | gain of function |
Gene Variant Descriptions | KIT W557_K558del results in the deletion of 2 amino acids in the juxtamembrane domain (exon 11) of the Kit protein from amino acids 557 to 558 (PMID: 12918066). W557_K558del results in constitutive activation of Kit and increased Erk phosphorylation, and leads to increased invasiveness and expression of ETV1 in cell culture (PMID: 25239608, PMID: 26936919). |
Associated Drug Resistance | |
Category Variants Paths |
KIT mutant KIT act mut KIT exon 11 del KIT W557_K558del KIT mutant KIT exon11 KIT exon 11 del KIT W557_K558del |
Transcript | NM_000222.3 |
gDNA | chr4:g.54727437_54727442delTGGAAG |
cDNA | c.1669_1674delTGGAAG |
Protein | p.W557_K558delWK |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_000222.2 | chr4:g.54727437_54727442delTGGAAG | c.1669_1674delTGGAAG | p.W557_K558del | RefSeq | GRCh38/hg38 |
NM_000222.3 | chr4:g.54727437_54727442delTGGAAG | c.1669_1674delTGGAAG | p.W557_K558delWK | RefSeq | GRCh38/hg38 |
NM_000222 | chr4:g.54727437_54727442delTGGAAG | c.1669_1674delTGGAAG | p.W557_K558del | RefSeq | GRCh38/hg38 |
XM_017008178.1 | chr4:g.54727437_54727442delTGGAAG | c.1669_1674delTGGAAG | p.W557_K558del | RefSeq | GRCh38/hg38 |
NM_001385284.1 | chr4:g.54727434_54727439delCAGTGG | c.1669_1674delCAGTGG | p.Q557_W558delQW | RefSeq | GRCh38/hg38 |
NM_001093772.2 | chr4:g.54727449_54727454delGAGGAG | c.1669_1674delGAGGAG | p.E557_E558delEE | RefSeq | GRCh38/hg38 |
NM_001385285.1 | chr4:g.54727437_54727442delTGGAAG | c.1669_1674delTGGAAG | p.W557_K558delWK | RefSeq | GRCh38/hg38 |
XM_017008178 | chr4:g.54727437_54727442delTGGAAG | c.1669_1674delTGGAAG | p.W557_K558del | RefSeq | GRCh38/hg38 |
NM_001385288.1 | chr4:g.54727447_54727452delTTGAGG | c.1670_1675delTTGAGG | p.V557_E558delVE | RefSeq | GRCh38/hg38 |
NM_001385290.1 | chr4:g.54727434_54727439delCAGTGG | c.1669_1674delCAGTGG | p.Q557_W558delQW | RefSeq | GRCh38/hg38 |
NM_001385292.1 | chr4:g.54727447_54727452delTTGAGG | c.1670_1675delTTGAGG | p.V557_E558delVE | RefSeq | GRCh38/hg38 |
NM_001385286.1 | chr4:g.54727449_54727454delGAGGAG | c.1669_1674delGAGGAG | p.E557_E558delEE | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
KIT W557_K558del | Advanced Solid Tumor | sensitive | Ponatinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, transformed cells expressing KIT W557_K558del demonstrated sensitivity to treatment with Iclusig (ponatinib) in both culture and cell line xenograft models, resulting in reduced cell viability and near complete tumor regression (PMID: 25239608). | 25239608 |
KIT W557_K558del | Advanced Solid Tumor | sensitive | Sunitinib | Preclinical | Actionable | In a preclinical study, transformed cells expressing KIT W557_K558del demonstrated sensitivity to treatment with Sutent (sunitinib) in culture, resulting in reduced cell viability (PMID: 25239608). | 25239608 |
KIT W557_K558del | Advanced Solid Tumor | sensitive | Imatinib | Preclinical | Actionable | In a preclinical study, transformed cells expressing KIT W557_K558del demonstrated sensitivity to treatment with Gleevec (imatinib) in culture, resulting in reduced cell viability (PMID: 25239608). | 25239608 |
KIT W557_K558del | Advanced Solid Tumor | sensitive | Regorafenib | Preclinical | Actionable | In a preclinical study, transformed cells expressing KIT W557_K558del demonstrated sensitivity to treatment with Stivarga (regorafineb) in culture, resulting in reduced cell viability (PMID: 25239608). | 25239608 |
KIT W557_K558del | gastrointestinal stromal tumor | sensitive | PD-0325901 | Preclinical - Cell culture | Actionable | In a preclinical study, PD-0325901 treatment inhibited Erk phosphorylation and decreased expression of ETV1 and CXCR4 in gastrointestinal stromal tumor cells harboring KIT W557_K558del (PMID: 26936919). | 26936919 |
KIT W557_K558del | Advanced Solid Tumor | sensitive | Nilotinib | Preclinical - Cell culture | Actionable | In a preclinical study, Tasigna (nilotinib) inhibited growth of transformed cells expressing KIT W557_K558del in culture (PMID: 17699867). | 17699867 |
KIT W557_K558del | Advanced Solid Tumor | sensitive | Dasatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Sprycel (dasatinib) inhibited growth and induced apoptosis of transformed cells expressing KIT W557_K558del in culture (PMID: 17699867). | 17699867 |
KIT W557_K558del | Advanced Solid Tumor | sensitive | AZD3229 | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT W557_K558del demonstrated sensitivity to AZD3229 in culture, resulting in reduced cell viability (PMID: 32350132). | 32350132 |
KIT W557_K558del | 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 in culture, but was less potent compared to treatment with AZD3229 (PMID: 32350132). | 32350132 |
KIT W557_K558del | Advanced Solid Tumor | sensitive | Ripretinib | Preclinical - Cell culture | Actionable | In a preclinical study, Qinlock (ripretinib) treatment resulted in decreased viability of transformed cells expressing KIT W557_K558del in culture, but was less potent compared to treatment with AZD3229 (PMID: 32350132). | 32350132 |
KIT W557_K558del | Advanced Solid Tumor | sensitive | Cabozantinib | Preclinical - Cell culture | Actionable | In a preclinical study, Cometriq (Cabometyx, cabozantinib) treatment resulted in decreased viability of transformed cells expressing KIT W557_K558del in culture (PMID: 33212994). | 33212994 |
KIT W557_K558del | gastrointestinal stromal tumor | predicted - sensitive | Imatinib | Case Reports/Case Series | Actionable | In a clinical case study, Gleevec (imatinib) treatment resulted in 4 partial responses and 1 stable disease in 5 patients with gastrointestinal stromal tumors harboring KIT W557_K558del, with progression-free survival ranging from 12.2 to 36.5 months and overall survival ranging from 22.7 to 67.9 months (PMID: 18294292). | 18294292 |