KIT T670I
Gene Variant Detail

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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 T670X KIT T670I

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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_000222.3 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
NM_001385285.1 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 chr4:g.54729353C>T c.2009C>T p.T670I RefSeq GRCh38/hg38

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
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 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 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 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 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 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 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 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 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
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 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 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 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 predicted - sensitive IDRX-42 Preclinical - Biochemical Actionable In a preclinical study, IDRX-42 inhibited kinase activity of KIT T670I in an vitro assay (PMID: 40018846). 40018846