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Gene | KIT |
Variant | T670I |
Impact List | missense |
Protein Effect | gain of function |
Gene Variant Descriptions | KIT T670I lies within the ATP pocket in the protein kinase domain of the Kit protein (PMID: 15236194, PMID: 22355224). T670I confers a gain of function on Kit as indicated by constitutive Kit phosphorylation, is transforming in cultured cells, and is associated with resistance to Kit inhibitors (PMID: 17699867, PMID: 15236194). |
Associated Drug Resistance | Y |
Category Variants Paths |
KIT mutant KIT act mut KIT T670I KIT mutant KIT exon14 KIT T670I |
Transcript | NM_000222.3 |
gDNA | chr4:g.54729353C>T |
cDNA | c.2009C>T |
Protein | p.T670I |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
XM_017008178 | chr4:g.54729353C>T | c.2009C>T | p.T670I | RefSeq | GRCh38/hg38 |
NM_000222 | chr4:g.54729353C>T | c.2009C>T | p.T670I | RefSeq | GRCh38/hg38 |
NM_000222.2 | chr4:g.54729353C>T | c.2009C>T | p.T670I | RefSeq | GRCh38/hg38 |
XM_017008178.1 | chr4:g.54729353C>T | c.2009C>T | p.T670I | RefSeq | GRCh38/hg38 |
NM_000222.3 | chr4:g.54729353C>T | c.2009C>T | p.T670I | RefSeq | GRCh38/hg38 |
NM_001385285.1 | chr4:g.54729353C>T | c.2009C>T | p.T670I | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
KIT T670I | Advanced Solid Tumor | sensitive | Axitinib | Preclinical - Cell culture | Actionable | In a preclinical study, Inlyta (axitinib) inhibited KIT phosphorylation and proliferation of transformed cells expressing KIT T670I in culture, however, with decreased potency compared to its potency against other KIT variants (PMID: 31205508). | 31205508 |
KIT T670I | melanoma | resistant | Dasatinib | Preclinical | Actionable | In a preclinical study, melanoma cells expressing KIT T670I demonstrated resistance to treatment with Sprycel (dasatinib) (PMID: 23582185, PMID: 25594040). | 23582185 25594040 |
KIT T670I | melanoma | resistant | Imatinib | Preclinical | Actionable | In a preclinical study, melanoma cells expressing KIT T670I demonstrated resistance to treatment with Gleevec (imatinib mesylate) (PMID: 23582185, PMID: 25594040). | 23582185 25594040 |
KIT T670I | gastrointestinal stromal tumor | predicted - resistant | Imatinib | Case Reports/Case Series | Actionable | In a clinical case report, a patient with a gastrointestinal stromal tumor developed disease progression while being treated with Gleevec (imatinib), demonstrating a KIT T670I mutation in the progressive lesion (PMID: 15236194). | 15236194 |
KIT T670I | Advanced Solid Tumor | resistant | Imatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT T670I demonstrated resistance to Gleevec (imatinib) in culture (PMID: 35194937). | 35194937 |
KIT T670I | Advanced Solid Tumor | resistant | Imatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT T670I were resistant to treatment with Gleevec (imatinib) in culture (PMID: 33212994). | 33212994 |
KIT T670I | melanoma | resistant | Nilotinib | Preclinical | Actionable | In a preclinical study, melanoma cells expressing KIT T670I demonstrated resistance to treatment with Tasigna (nilotinib) (PMID: 23582185, PMID: 25594040). | 23582185 25594040 |
KIT T670I | Advanced Solid Tumor | sensitive | Nintedanib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Ofev (nintedanib) inhibited Kit autophosphorylation and proliferation of transformed cells expressing KIT T670I in culture, and suppressed tumor growth in cell line xenograft models (PMID: 35194937). | 35194937 |
KIT T670I | Advanced Solid Tumor | sensitive | Ponatinib | Preclinical | Actionable | In a preclinical study, cells expressing KIT T670I demonstrated sensitivity to Iclusig (ponatinib) in an in vitro kinase assay (PMID: 25239608). | 25239608 |
KIT T670I | Advanced Solid Tumor | sensitive | Regorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT T670I demonstrated sensitivity to Stivarga (regorafenib) treatment in culture, resulting in reduced cell viability (PMID: 33212994). | 33212994 |
KIT T670I | melanoma | sensitive | Sunitinib | Preclinical | Actionable | In a preclinical study, Sutent (sunitinib) demonstrated efficacy by inhibiting proliferation of cultured melanoma cells expressing KIT T670I (PMID: 23582185, PMID: 25594040). | 23582185 25594040 |
KIT T670I | Advanced Solid Tumor | sensitive | Sunitinib | Preclinical - Cell culture | Actionable | In a preclinical study, Sutent (sunitinib) inhibited proliferation of transformed cells expressing KIT T670I in culture (PMID: 31205508). | 31205508 |
KIT T670I | Advanced Solid Tumor | sensitive | Sunitinib | Preclinical - Cell culture | Actionable | In a preclinical study, Sutent (sunitinib) inhibited proliferation of transformed cells expressing KIT T670I in culture (PMID: 35194937). | 35194937 |
KIT T670I | Advanced Solid Tumor | sensitive | Sunitinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT T670I demonstrated sensitivity to Sutent (sunitinib) treatment in culture, resulting in reduced cell viability (PMID: 33212994). | 33212994 |
KIT T670I | Advanced Solid Tumor | sensitive | Cabozantinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT T670I demonstrated sensitivity to Cometriq (Cabometyx, cabozantinib) treatment in culture, resulting in reduced cell viability (PMID: 33212994). | 33212994 |
KIT T670I | gastrointestinal stromal tumor | predicted - resistant | Avapritinib | Phase I | Actionable | In a Phase I trial, patients with gastrointestinal stromal tumors harboring either KIT V654A or KIT T670I demonstrated decreased overall response rate (0%, 0/25 vs. 26%, 22/84) and increased progressive disease rate (72% vs 23%) compared to those without either KIT mutation when treated with Ayvakit (avapritinib) (PMID: 31270078; NCT02508532). | 31270078 |