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Gene | KIT |
Variant | V560_Y578del |
Impact List | deletion |
Protein Effect | gain of function - predicted |
Gene Variant Descriptions | KIT V560_Y578del results in the deletion of 18 amino acids in the juxtamembrane domain (exon 11) of the Kit protein from amino acids 560 to 578 (PMID: 16226710). V560_Y578del has not been characterized, however similar Kit exon 11 deletions are activating (PMID: 9438854, PMID: 15365079), and therefore, is predicted to lead to a gain of Kit protein function. |
Associated Drug Resistance | |
Category Variants Paths |
KIT mutant KIT act mut KIT exon 11 del KIT V560_Y578del KIT mutant KIT exon11 KIT exon 11 del KIT V560_Y578del |
Transcript | NM_000222.3 |
gDNA | chr4:g.54727447_54727503del57 |
cDNA | c.1679_1735del57 |
Protein | p.V560_Y578del19 |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
XM_017008180.1 | chr4:g.54727458_54727514del57 | c.1678_1734del57 | p.N560_W578del19 | RefSeq | GRCh38/hg38 |
NM_001385286.1 | chr4:g.54727458_54727514del57 | c.1678_1734del57 | p.N560_W578del19 | RefSeq | GRCh38/hg38 |
NM_001093772.1 | chr4:g.54727458_54727514del57 | c.1678_1734del57 | p.N560_W578del19 | RefSeq | GRCh38/hg38 |
XM_005265741.1 | chr4:g.54727443_54727499del57 | c.1678_1734del57 | p.V560_P578del19 | RefSeq | GRCh38/hg38 |
XM_005265742.3 | chr4:g.54727455_54727511del57 | c.1678_1734del57 | p.I560_K578del19 | RefSeq | GRCh38/hg38 |
XM_005265741 | chr4:g.54727443_54727499del57 | c.1678_1734del57 | p.V560_P578del19 | RefSeq | GRCh38/hg38 |
XM_017008180 | chr4:g.54727458_54727514del57 | c.1678_1734del57 | p.N560_W578del19 | RefSeq | GRCh38/hg38 |
XM_005265742 | chr4:g.54727455_54727511del57 | c.1678_1734del57 | p.I560_K578del19 | RefSeq | GRCh38/hg38 |
NM_001093772 | chr4:g.54727458_54727514del57 | c.1678_1734del57 | p.N560_W578del19 | RefSeq | GRCh38/hg38 |
XM_017008178.1 | chr4:g.54727447_54727503del57 | c.1679_1735del57 | p.V560_Y578del19 | RefSeq | GRCh38/hg38 |
NM_000222 | chr4:g.54727447_54727503del57 | c.1679_1735del57 | p.V560_Y578del19 | RefSeq | GRCh38/hg38 |
XM_017008179 | chr4:g.54727455_54727511del57 | c.1678_1734del57 | p.I560_K578del19 | RefSeq | GRCh38/hg38 |
NM_000222.3 | chr4:g.54727447_54727503del57 | c.1679_1735del57 | p.V560_Y578del19 | RefSeq | GRCh38/hg38 |
NM_000222.2 | chr4:g.54727447_54727503del57 | c.1679_1735del57 | p.V560_Y578del19 | RefSeq | GRCh38/hg38 |
XM_017008179.1 | chr4:g.54727455_54727511del57 | c.1678_1734del57 | p.I560_K578del19 | RefSeq | GRCh38/hg38 |
NM_001385288.1 | chr4:g.54727455_54727511del57 | c.1678_1734del57 | p.I560_K578del19 | RefSeq | GRCh38/hg38 |
NM_001385285.1 | chr4:g.54727447_54727503del57 | c.1679_1735del57 | p.V560_Y578del19 | RefSeq | GRCh38/hg38 |
XM_005265740 | chr4:g.54727443_54727499del57 | c.1678_1734del57 | p.V560_P578del19 | RefSeq | GRCh38/hg38 |
XM_005265740.1 | chr4:g.54727443_54727499del57 | c.1678_1734del57 | p.V560_P578del19 | RefSeq | GRCh38/hg38 |
NM_001385292.1 | chr4:g.54727455_54727511del57 | c.1678_1734del57 | p.I560_K578del19 | RefSeq | GRCh38/hg38 |
NM_001385284.1 | chr4:g.54727443_54727499del57 | c.1678_1734del57 | p.V560_P578del19 | RefSeq | GRCh38/hg38 |
XM_017008178 | chr4:g.54727447_54727503del57 | c.1679_1735del57 | p.V560_Y578del19 | RefSeq | GRCh38/hg38 |
NM_001385290.1 | chr4:g.54727443_54727499del57 | c.1678_1734del57 | p.V560_P578del19 | RefSeq | GRCh38/hg38 |
NM_001093772.2 | chr4:g.54727458_54727514del57 | c.1678_1734del57 | p.N560_W578del19 | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
KIT V560_Y578del | gastrointestinal stromal tumor | sensitive | Axitinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Inlyta (axitinib) inhibited KIT phosphorylation and downstream signaling, reduced proliferation and induced cell-cycle arrest in a gastrointestinal stromal tumor cell line harboring KIT V560_Y578del in culture, and inhibited tumor growth in xenograft models (PMID: 31205508). | 31205508 |
KIT V560_Y578del | gastrointestinal stromal tumor | sensitive | Imatinib | Preclinical | Actionable | In a preclinical study, a patient derived GIST cell line harboring KIT V560_Y578del demonstrated sensitivity to Gleevec (imatinib) in culture (PMID: 25239608). | 25239608 |
KIT V560_Y578del | gastrointestinal stromal tumor | sensitive | Imatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Gleevec (imatinib) inhibited cell growth and KIT signaling in a gastrointestinal stromal tumor cell line harboring KIT V560_Y578del in culture, but was less potent compared to AZD3229 (PMID: 32350132). | 32350132 |
KIT V560_Y578del | gastrointestinal stromal tumor | sensitive | Nintedanib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Ofev (nintedanib) decreased Kit phosphorylation and downstream signaling, induced cell-cycle arrest and apoptosis, and inhibited proliferation of a gastrointestinal stromal tumor cell line harboring KIT V560_Y578del in culture, and suppressed tumor growth in cell line xenograft models (PMID: 35194937). | 35194937 |
KIT V560_Y578del | gastrointestinal stromal tumor | sensitive | Ponatinib | Preclinical - Patient cell culture | Actionable | In a preclinical study, a patient-derived gastrointestinal stromal tumor (GIST) cell line harboring KIT V560_Y578del demonstrated sensitivity to Iclusig (ponatinib) in culture (PMID: 25239608). | 25239608 |
KIT V560_Y578del | gastrointestinal stromal tumor | sensitive | Regorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Stivarga (regorafenib) inhibited growth of a gastrointestinal stromal tumor cell line harboring KIT V560_Y578del in culture, but was less potent compared to AZD3229 (PMID: 32350132). | 32350132 |
KIT V560_Y578del | gastrointestinal stromal tumor | sensitive | Sunitinib | Preclinical - Cell culture | Actionable | In a preclinical study, Sutent (sunitinib) inhibited proliferation of a gastrointestinal stromal tumor cell line harboring KIT V560_Y578del in culture (PMID: 31205508). | 31205508 |
KIT V560_Y578del | gastrointestinal stromal tumor | sensitive | Copanlisib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Aliqopa (copanlisib) inhibited cell growth and PI3K signaling in a gastrointestinal stromal tumor cell line harboring KIT V560_Y578del in culture, and inhibited tumor growth in cell line xenograft models (PMID: 32371592). | 32371592 |
KIT V560_Y578del | gastrointestinal stromal tumor | sensitive | Imatinib + Infigratinib | Preclinical - Cell culture | Actionable | In a preclinical study, Truseltiq (infigratinib) and Gleevec (imatinib) combination treatment demonstrated enhanced antiproliferative activity in gastrointestinal stromal tumor cells harboring KIT V560_Y578del in culture (PMID: 25673643). | 25673643 |
KIT V560_Y578del | gastrointestinal stromal tumor | sensitive | Avapritinib | Preclinical - Cell culture | Actionable | In a preclinical study, Ayvakit (avapritinib) inhibited cell growth and KIT signaling in a gastrointestinal stromal tumor cell line harboring KIT V560_Y578del in culture, but was less potent compared to AZD3229 (PMID: 32350132). | 32350132 |
KIT V560_Y578del | gastrointestinal stromal tumor | resistant | Ripretinib | Preclinical - Cell culture | Actionable | In a preclinical study, Qinlock (ripretinib) inhibited cell growth and KIT signaling in a gastrointestinal stromal tumor cell line harboring KIT V560_Y578del in culture, but was less potent compared to AZD3229 (PMID: 32350132). | 32350132 |
KIT V560_Y578del | gastrointestinal stromal tumor | sensitive | AZD3229 | Preclinical - Cell culture | Actionable | In a preclinical study, AZD3229 inhibited cell growth and KIT signaling in a gastrointestinal stromal tumor cell line harboring KIT V560_Y578del in culture (PMID: 32350132). | 32350132 |
KIT V560_Y578del | gastrointestinal stromal tumor | sensitive | Olverembatinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Olverembatinib (HQP1351) treatment inhibited Kit activity and proliferation of a gastrointestinal stromal tumor (GIST) cell line harboring KIT V560_Y578del in culture, and inhibited tumor growth in a cell line xenograft model (PMID: 31673329). | 31673329 |
KIT V560_Y578del | gastrointestinal stromal tumor | sensitive | Copanlisib + Imatinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, the combination of Aliqopa (copanlisib) and Gleevec (imatinib) demonstrated enhanced cell growth inhibition and increased apoptosis of gastrointestinal stromal tumor cells harboring KIT V560_Y578del in culture and in cell line xenograft models (PMID: 32371592). | 32371592 |