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Gene | KIT |
Variant | W557Lfs*5 |
Impact List | frameshift |
Protein Effect | loss of function - predicted |
Gene Variant Descriptions | KIT W557Lfs*5 indicates a shift in the reading frame starting at amino acid 557 and terminating 5 residues downstream causing a premature truncation of the 976 amino acid Kit protein (UniProt.org). Due to the loss of the protein kinase domain (UniProt.org), W557Lfs*5 is predicted to lead to a loss of Kit protein function. |
Associated Drug Resistance | |
Category Variants Paths |
KIT mutant KIT exon11 KIT W557Lfs*5 |
Transcript | NM_000222.3 |
gDNA | chr4:g.54727437dupT |
cDNA | c.1669dupT |
Protein | p.W557Lfs*5 |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_000222 | chr4:g.54727436_54727437insC | c.1668_1669insC | p.W557Lfs*5 | RefSeq | GRCh38/hg38 |
NM_000222.2 | chr4:g.54727437dupT | c.1669dupT | p.W557Lfs*5 | RefSeq | GRCh38/hg38 |
NM_000222.3 | chr4:g.54727437dupT | c.1669dupT | p.W557Lfs*5 | RefSeq | GRCh38/hg38 |
XM_017008178.1 | chr4:g.54727437dupT | c.1669dupT | p.W557Lfs*5 | RefSeq | GRCh38/hg38 |
NM_001385285.1 | chr4:g.54727437dupT | c.1669dupT | p.W557Lfs*5 | RefSeq | GRCh38/hg38 |
XM_017008178 | chr4:g.54727436_54727437insC | c.1668_1669insC | p.W557Lfs*5 | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
KIT W557Lfs*5 KIT P577del KIT D820G | gastrointestinal stromal tumor | resistant | Imatinib | Preclinical - Pdx | Actionable | In a preclinical study, a gastrointestinal stromal tumor patient-derived xenograft (PDX) model harboring KIT P577del, KIT W557Lfs*5, and KIT D820G demonstrated resistance to treatment with Gleevec (imatinib) (PMID: 27777285). | 27777285 |
KIT W557Lfs*5 KIT P577del KIT D820G | gastrointestinal stromal tumor | sensitive | Cabozantinib | Preclinical - Pdx | Actionable | In a preclinical study, Cometriq (Cabometyx, cabozantinib) slowed tumor growth and decreased mitotic activity in a gastrointestinal stromal tumor patient-derived xenograft (PDX) model harboring KIT P577del, KIT W557Lfs*5, and KIT D820G (PMID: 27777285). | 27777285 |
KIT W557Lfs*5 KIT P577del KIT D820G | gastrointestinal stromal tumor | sensitive | PLX9486 | Preclinical - Pdx | Actionable | In a preclinical study, PLX9486 treatment decreased Mapk phosphorylation and Kit downstream signaling, inhibited proliferation, and reduced tumor growth in a Gleevec (imatinib)-resistant patient-derived xenograft (PDX) model of gastrointestinal stromal tumor harboring KIT P577del, W557Lfs*5, and D820G (PMID: 30523507). | 30523507 |
KIT W557Lfs*5 KIT P577del KIT D820G | gastrointestinal stromal tumor | sensitive | Avapritinib | Preclinical - Pdx | Actionable | In a preclinical study, a patient derived xenograft (PDX) model with a gastrointestinal stromal tumor harboring KIT W557Lfs*5, KIT P577del, and KIT D820G was sensitive to treatment with Ayvakit (avapritinib), demonstrating a stabilized tumor volume at a dose of 10mg/kg and 27% tumor regression at a dose of 30mg/kg, a histologic response, and apoptotic activity (PMID: 30274985). | 30274985 |
KIT W557Lfs*5 KIT P577del KIT D820G | gastrointestinal stromal tumor | predicted - sensitive | IDRX-42 | Preclinical - Pdx | Actionable | In a preclinical study, IDRX-42 treatment inhibited mitosis and decreased tumor growth in a patient-derived xenograft (PDX) model of gastrointestinal stromal tumor harboring KIT P577del, W557Lfs*5, and D820G (Cancer Res 2022;82(12_Suppl):Abstract nr 2666). | detail... |
KIT W557Lfs*5 KIT P577del KIT D820G | gastrointestinal stromal tumor | predicted - sensitive | Dovitinib | Preclinical - Pdx | Actionable | In preclinical study, Dovitinib (TKI258) treatment stabilized tumor volume in a patient-derived xenograft (PDX) model of gastrointestinal stromal tumor harboring KIT P577del, KIT W557Lfs*5, and KIT D820G (PMID: 35625872). | 35625872 |