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Gene | KIT |
Variant | N655K |
Impact List | missense |
Protein Effect | gain of function - predicted |
Gene Variant Descriptions | KIT N655K lies within tyrosine kinase domain 1 (exon 13) of the Kit protein (PMID: 17555444). N655K results in constitutive phosphorylation of Kit in cell culture (PMID: 17489795), 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 N655K KIT mutant KIT exon13 KIT N655K |
Transcript | NM_000222.3 |
gDNA | chr4:g.54728096T>G |
cDNA | c.1965T>G |
Protein | p.N655K |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_001385285.1 | chr4:g.54728096T>G | c.1965T>G | p.N655K | RefSeq | GRCh38/hg38 |
NM_000222 | chr4:g.54728096T>G | c.1965T>G | p.N655K | RefSeq | GRCh38/hg38 |
NM_000222.3 | chr4:g.54728096T>G | c.1965T>G | p.N655K | RefSeq | GRCh38/hg38 |
NM_000222.2 | chr4:g.54728096T>G | c.1965T>G | p.N655K | RefSeq | GRCh38/hg38 |
XM_017008178 | chr4:g.54728096T>G | c.1965T>G | p.N655K | RefSeq | GRCh38/hg38 |
XM_017008178.1 | chr4:g.54728096T>G | c.1965T>G | p.N655K | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
KIT N655K | Advanced Solid Tumor | predicted - sensitive | Imatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT N655K demonstrated some sensitivity to Gleevec (imatinib) treatment in culture, resulting in reduced cell viability at high treatment dosages (PMID: 33212994). | 33212994 |
KIT N655K | Advanced Solid Tumor | decreased response | Sunitinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT N655K demonstrated a reduced response to Sutent (sunitinib) treatment compared to cells expressing KIT T670I in culture (PMID: 33212994). | 33212994 |
KIT N655K | Advanced Solid Tumor | decreased response | Regorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT N655K demonstrated a reduced response to Stivarga (regorafenib) treatment compared to cells expressing KIT T670I in culture (PMID: 33212994). | 33212994 |
KIT N655K | Advanced Solid Tumor | decreased response | Cabozantinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT N655K demonstrated a reduced response to Cometriq (Cabometyx, cabozantinib) treatment compared to cells expressing KIT T670I in culture (PMID: 33212994). | 33212994 |
KIT N655K | Advanced Solid Tumor | predicted - sensitive | Avapritinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT N655K demonstrated some sensitivity to Ayvakit (avapritinib) in culture, but were less sensitive than cells expressing KIT W557_K558del (PMID: 33212994). | 33212994 |
KIT N655K | Advanced Solid Tumor | predicted - sensitive | Ripretinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT N655K demonstrated some sensitivity to Qinlock (ripretinib) treatment in culture, but were less sensitive than cells expressing KIT W557_K558del (PMID: 33212994). | 33212994 |
KIT N655K | gastrointestinal stromal tumor | predicted - sensitive | Imatinib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with gastrointestinal stromal tumor (GIST) harboring a germline KIT N655K mutation, associated with hereditary GIST syndrome, demonstrated slow disease progression for 12 months while on treatment with Gleevec (imatinib) at 400mg/d, and upon disease progression following surgery and 15 months of Sutent (sunitinib) treatment, was rechallenged with Gleevec (imatinib) at 800mg/d and remained stable for a further 9 months (PMID: 33212994). | 33212994 |