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 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
XM_017008178.1 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
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 W557_K558del KIT T670I Advanced Solid Tumor sensitive Ponatinib Preclinical Actionable In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT T670I demonstrated sensitivity to treatment with Iclusig (ponatinib) in both culture and cell line xenograft models, resulting in reduced cell viability and decreased tumor volume (PMID: 25239608). 25239608
KIT W557_K558del KIT T670I Advanced Solid Tumor sensitive Sunitinib Preclinical - Cell line xenograft Actionable In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT T670I demonstrated sensitivity to treatment with Sutent (sunitinib) in both culture and cell line xenograft models, resulting in reduced cell viability, decreased tumor volume, and tumor regression (PMID: 25239608). 25239608
KIT W557_K558del KIT T670I Advanced Solid Tumor no benefit Imatinib Preclinical - Cell line xenograft Actionable In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT T670I demonstrated no response to treatment with Gleevec (imatinib) in both culture and xenograft models (PMID: 25239608). 25239608
KIT W557_K558del KIT T670I Advanced Solid Tumor decreased response Regorafenib Preclinical Actionable In a preclinical study, transformed cells co-expressing KIT W557_K558del and KIT T670I demonstrated a decreased response to treatment with Stivarga (regorafenib) compared to cells expressing KIT W557_K558del alone in culture (PMID: 25239608). 25239608
KIT W557_K558del KIT T670I Advanced Solid Tumor decreased response Regorafenib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT W557_K558del and KIT T670I demonstrated a decreased response to treatment with Stivarga (regorafenib) compared to cells expressing KIT W557_K558del alone in culture (PMID: 32350132). 32350132
KIT W557_K558del KIT T670I Advanced Solid Tumor resistant Dasatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing a KIT W557_K558del/T670I double mutation demonstrated resistance to Sprycel (dasatinib) in culture (PMID: 17699867). 17699867
KIT W557_K558del KIT T670I Advanced Solid Tumor resistant Nilotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing a KIT W557_K558del/T670I double mutation demonstrated resistance to Tasigna (nilotinib) in culture (PMID: 17699867). 17699867
KIT W557_K558del KIT T670I Advanced Solid Tumor sensitive Sorafenib Preclinical - Cell culture Actionable In a preclinical study, Nexavar (sorafenib) inhibited proliferation and induced apoptosis of transformed cells expressing a KIT W557_K558del/T670I double mutation in culture (PMID: 17699867). 17699867
KIT W557_K558del KIT T670I Advanced Solid Tumor sensitive AZD3229 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT W557_K558del and KIT T670I demonstrated sensitivity to AZD3229 in culture, resulting in reduced cell viability (PMID: 32350132). 32350132
KIT W557_K558del KIT T670I Advanced Solid Tumor resistant Avapritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT W557_K558del and KIT T670I demonstrated resistance to Ayvakit (avapritinib) in culture (PMID: 32350132). 32350132
KIT W557_K558del KIT T670I Advanced Solid Tumor decreased response Ripretinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT W557_K558del and KIT T670I demonstrated a decreased response to treatment with Qinlock (ripretinib) compared to cells expressing KIT W557_K558del alone in culture (PMID: 32350132). 32350132
KIT W557_K558del KIT T670I gastrointestinal stromal tumor predicted - resistant Imatinib Case Reports/Case Series Actionable In a clinical case study, a patient with gastrointestinal stromal tumor harboring KIT W557_K558del progressed following an initial response to Gleevec (imatinib), and was found to have acquired the secondary resistance mutation KIT T670I (PMID: 18294292). 18294292
KIT V560_Y578del KIT T670I gastrointestinal stromal tumor sensitive Ponatinib Preclinical Actionable In a preclinical study, a patient derived GIST cell line co-harboring KIT V560_Y578del and KIT T670I demonstrated sensitivity to treatment with Iclusig (ponatinib) (PMID: 25239608). 25239608
KIT V560_Y578del KIT T670I gastrointestinal stromal tumor sensitive Sunitinib Preclinical - Cell culture Actionable In a preclinical study, a patient-derived gastrointestinal stromal tumor (GIST) cell line co-harboring KIT V560_Y578del and KIT T670I demonstrated sensitivity to treatment with Sutent (sunitinib) (PMID: 25239608). 25239608
KIT V560_Y578del KIT T670I 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 and KIT T670I in culture (PMID: 31205508). 31205508
KIT V560_Y578del KIT T670I 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 and KIT T670I in culture, and inhibited tumor growth in xenograft models (PMID: 31205508). 31205508
KIT V560_Y578del KIT T670I 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 and KIT T670I in culture, and inhibited tumor growth in cell line xenograft models (PMID: 32371592). 32371592
KIT V560_Y578del KIT T670I gastrointestinal stromal tumor predicted - 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 but did not result in increased apoptosis of gastrointestinal stromal tumor cells harboring KIT V560_Y578del and KIT T670I in culture, and did not result in increased tumor growth inhibition compared to Aliqopa (copanlisib) alone in cell line xenograft models (PMID: 32371592). 32371592
KIT V560_Y578del KIT T670I 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 and T670I in culture, and suppressed tumor growth in cell line xenograft models (PMID: 35194937). 35194937
KIT V560D KIT T670I Advanced Solid Tumor sensitive Motesanib Diphosphate Preclinical - Cell culture Actionable In a preclinical study, Motesanib (AMG 706) inhibited KIT phosphorylation and growth of cells expressing a KIT V560D/T670I double mutation in culture (PMID: 20633291). 20633291
KIT V560D KIT T670I Advanced Solid Tumor resistant Flumatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing KIT V560D and KIT T670I were resistant to Flumatinib in culture (PMID: 24205792). 24205792
KIT V559D 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 and KIT V559D in culture (PMID: 31205508). 31205508
KIT V559D KIT T670I Advanced Solid Tumor sensitive Sunitinib Preclinical - Cell culture Actionable In a preclinical study, Sutent (sunitinib) inhibited proliferation of transformed cells expressing KIT V559D and T670I in culture (PMID: 35194937). 35194937
KIT V559D KIT T670I Advanced Solid Tumor sensitive Sunitinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing KIT V559D and KIT T670I were sensitive to treatment with Sutent (sunitinib) in culture, demonstrating decreased cell proliferation (PMID: 24205792). 24205792
KIT V559D KIT T670I Advanced Solid Tumor sensitive Nintedanib Preclinical - Cell culture Actionable In a preclinical study, Ofev (nintedanib) inhibited proliferation of transformed cells expressing KIT V559D and T670I in culture (PMID: 35194937). 35194937
KIT V559D KIT T670I Advanced Solid Tumor resistant Avapritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT V559D and T670I were resistant to Ayvakit (avapritinib) treatment in culture (PMID: 35194937). 35194937
KIT V559D KIT T670I Advanced Solid Tumor resistant Imatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT V559D and T670I were resistant to Gleevec (imatinib) treatment in culture (PMID: 35194937). 35194937
KIT V559D KIT T670I Advanced Solid Tumor resistant Ripretinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT V559D and T670I were resistant to Qinlock (ripretinib) treatment in culture (PMID: 35194937). 35194937
KIT exon11 KIT T670I gastrointestinal stromal tumor resistant Imatinib Preclinical - Pdx Actionable In a preclinical study, Gleevec (imatinib mesylate) did not inhibit Kit, Erk signaling and resulted in limited (53.9%) tumor inhibition in patient-derived xenograft (PDX) model of gastrointestinal stromal tumor harboring KIT exon 11 mutation (K550_splice) and KIT T670I, which was established from a patient who did not respond to Gleevec (imatinib mesylate) (PMID: 29100343). 29100343
KIT exon11 KIT T670I gastrointestinal stromal tumor predicted - sensitive Sunitinib Preclinical - Pdx Actionable In a preclinical study, Sutent (sunitinib) inhibited Kit signaling, resulted in 86.7% tumor growth inhibition in patient-derived xenograft (PDX) model of gastrointestinal stromal tumor harboring KIT exon 11 mutation (K550_splice) and KIT T670I, which was established from a patient who did not respond to Gleevec (imatinib mesylate) (PMID: 29100343). 29100343
KIT exon11 KIT T670I gastrointestinal stromal tumor predicted - sensitive Regorafenib Preclinical - Pdx Actionable In a preclinical study, Stivarga (regorafenib) inhibited Kit signaling, resulted in tumor growth inhibition in patient-derived xenograft (PDX) model of gastrointestinal stromal tumor harboring KIT exon 11 mutation (K550_splice) and KIT T670I, which was established from a patient who did not respond to Gleevec (imatinib mesylate) (PMID: 29100343). 29100343
KIT T670I KIT D816V Advanced Solid Tumor decreased response Midostaurin Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing KIT D816V and KIT T670I demonstrated a decreased response compared to cells expressing KIT D816V alone when treated with Rydapt (midostaurin) in culture (PMID: 31270078). 31270078
KIT T670I KIT D816V Advanced Solid Tumor resistant Avapritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing KIT D816V and KIT T670I demonstrated resistance to treatment with Ayvakit (avapritinib) in culture (PMID: 31270078). 31270078
KIT exon 11 del KIT T670I gastrointestinal stromal tumor decreased response Ripretinib Preclinical - Cell culture Actionable In a preclinical study, gastrointestinal stromal tumor cells harboring both KIT exon 11 deletion and KIT T670I demonstrated reduced response to growth inhibition by Qinlock (ripretinib) compared to cells harboring KIT exon 11 deletion alone in culture (PMID: 31085175). 31085175
KIT exon 11 del KIT T670I gastrointestinal stromal tumor resistant Imatinib Preclinical - Cell culture Actionable In a preclinical study, gastrointestinal stromal tumor cells harboring both KIT exon 11 deletion and KIT T670I were resistant to Gleevec (imatinib) in culture (PMID: 31085175). 31085175
KIT exon 11 del KIT T670I gastrointestinal stromal tumor sensitive Sunitinib Preclinical - Cell culture Actionable In a preclinical study, Sutent (sunitinib) inhibited proliferation of gastrointestinal stromal tumor cells harboring both KIT exon 11 deletion and KIT T670I in culture (PMID: 31085175). 31085175
KIT exon 11 del KIT T670I gastrointestinal stromal tumor sensitive Regorafenib Preclinical - Cell culture Actionable In a preclinical study, Stivarga (regorafenib) inhibited proliferation of gastrointestinal stromal tumor cells harboring both KIT exon 11 deletion and KIT T670I in culture (PMID: 31085175). 31085175
KIT exon 11 del KIT T670I gastrointestinal stromal tumor sensitive Midostaurin Preclinical - Cell culture Actionable In a preclinical study, Rydapt (midostaurin) inhibited proliferation of gastrointestinal stromal tumor cells harboring both KIT exon 11 deletion and KIT T670I in culture (PMID: 31085175). 31085175
KIT exon 11 del KIT T670I gastrointestinal stromal tumor sensitive Avapritinib Preclinical - Cell culture Actionable In a preclinical study, Ayvakit (avapritinib) inhibited proliferation of gastrointestinal stromal tumor cells harboring both KIT exon 11 deletion and KIT T670I in culture (PMID: 31085175). 31085175
KIT exon 11 del KIT T670I Advanced Solid Tumor predicted - sensitive THE-630 Preclinical - Cell culture Actionable In a preclinical study, THE-630 treatment inhibited growth of cells co-expressing a KIT exon 11 deletion and KIT T670I in culture (Cancer Res 2021;81(13_Suppl):Abstract nr 1292). detail...
CTNNB1 mut KIT V559D KIT T670I hepatocellular carcinoma predicted - sensitive WNTinib Preclinical - Cell culture Actionable In a preclinical study, a hepatocellular carcinoma cell line harboring a deletion of CTNNB1 exons and expressing KIT V559D and T670I was resistant to WNTinib in culture (PMID: 37537299). 37537299