KIT T670I: Gene Variant Detail - Cancer Knowledgebase (CKB)

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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

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Showing 1 to 6 of 6 entries

Transcript	gDNA	cDNA	Protein	Source Database	Genome Build
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
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
XM_017008178	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

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Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
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	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	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	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	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	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	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

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KIT T670IGene Variant Detail

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KIT T670I
Gene Variant Detail