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Gene | KIT |
Variant | D419del |
Impact List | deletion |
Protein Effect | unknown |
Gene Variant Descriptions | KIT D419del results in the deletion of an amino acid in Ig-like C2-type domain 5 of the Kit protein at amino acid 419 (UniProt.org). The functional effect of D419del is conflicting, as D419del has been reported to result in ligand-independent phosphorylation of Kit (PMID: 16143141, PMID: 15618474), and to result in lack of Kit phosphorylation and lack of cytokine-independent growth in cell culture (PMID: 31182436), and leads to Kit inactivation in response to Ptpre similar to wild-type Kit in cultured cells (PMID: 33732906). |
Associated Drug Resistance | |
Category Variants Paths |
KIT mutant KIT exon8 KIT D419del |
Transcript | NM_000222.3 |
gDNA | chr4:g.54723607_54723609delGAC |
cDNA | c.1255_1257delGAC |
Protein | p.D419del |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_001385286.1 | chr4:g.54723607_54723609delGAC | c.1255_1257delGAC | p.D419del | RefSeq | GRCh38/hg38 |
XM_017008178.1 | chr4:g.54723607_54723609delGAC | c.1255_1257delGAC | p.D419del | RefSeq | GRCh38/hg38 |
NM_001093772.2 | chr4:g.54723607_54723609delGAC | c.1255_1257delGAC | p.D419del | RefSeq | GRCh38/hg38 |
XM_017008178 | chr4:g.54723607_54723609delGAC | c.1255_1257delGAC | p.D419del | RefSeq | GRCh38/hg38 |
NM_001093772.2 | chr4:g.54723607_54723609delGAC | c.1255_1257delGAC | p.D419del | RefSeq | GRCh38/hg38 |
NM_000222.3 | chr4:g.54723607_54723609delGAC | c.1255_1257delGAC | p.D419del | RefSeq | GRCh38/hg38 |
XM_017008180 | chr4:g.54723607_54723609delGAC | c.1255_1257delGAC | p.D419del | RefSeq | GRCh38/hg38 |
NM_000222.2 | chr4:g.54723607_54723609delGAC | c.1255_1257delGAC | p.D419del | RefSeq | GRCh38/hg38 |
NM_001093772 | chr4:g.54723607_54723609delGAC | c.1255_1257delGAC | p.D419del | RefSeq | GRCh38/hg38 |
NM_000222 | chr4:g.54723607_54723609delGAC | c.1255_1257delGAC | p.D419del | RefSeq | GRCh38/hg38 |
NM_001093772.1 | chr4:g.54723607_54723609delGAC | c.1255_1257delGAC | p.D419del | RefSeq | GRCh38/hg38 |
NM_001385285.1 | chr4:g.54723607_54723609delGAC | c.1255_1257delGAC | p.D419del | RefSeq | GRCh38/hg38 |
XM_017008180.1 | chr4:g.54723607_54723609delGAC | c.1255_1257delGAC | p.D419del | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
KIT D419del | hematologic cancer | no benefit | Crenolanib | Preclinical - Cell culture | Actionable | In a preclinical study, cells expressing KIT D419del did not respond to treatment with Crenolanib in culture (PMID: 31182436). | 31182436 |
KIT D419del | hematologic cancer | no benefit | Dasatinib | Preclinical - Cell culture | Actionable | In a preclinical study, cells expressing KIT D419del did not respond to treatment with Sprycel (dasatinib) in culture (PMID: 31182436). | 31182436 |
KIT D419del | mastocytosis | predicted - sensitive | Imatinib | Case Reports/Case Series | Actionable | In a clinical case study, Gleevec (imatinib) treatment resolved symptoms and stopped disease progression after 32 months in a pediatric patient with progressive cutaneous mastocytosis harboring a somatic KIT D419del and a germline S840N mutation (PMID: 18567837). | 18567837 |
KIT D419del | Advanced Solid Tumor | predicted - sensitive | Imatinib | Preclinical - Biochemical | Actionable | In a preclinical study, Gleevec (imatinib) treatment inhibited Kit autophosphorylation in transformed cells expressing KIT D419del in culture (PMID: 16143141). | 16143141 |