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Gene | ALK |
Variant | I1171T |
Impact List | missense |
Protein Effect | gain of function |
Gene Variant Descriptions | ALK I1171T lies within the protein kinase domain of the Alk protein (UniProt.org). I1171T confers a gain of function on the Alk protein as indicated by ligand-independent autophosphorylation, activation of Erk1/2, and cell transformation (PMID: 29907598), and has been demonstrated to confer drug resistance in the context of ALK fusions in culture (PMID: 27009859). |
Associated Drug Resistance | Y |
Category Variants Paths |
ALK mutant ALK act mut ALK I1171T ALK mutant ALK I1171X ALK I1171T |
Transcript | NM_004304.5 |
gDNA | chr2:g.29222347A>G |
cDNA | c.3512T>C |
Protein | p.I1171T |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_004304 | chr2:g.29222347A>G | c.3512T>C | p.I1171T | RefSeq | GRCh38/hg38 |
NM_004304.5 | chr2:g.29222347A>G | c.3512T>C | p.I1171T | RefSeq | GRCh38/hg38 |
NM_004304.4 | chr2:g.29222347A>G | c.3512T>C | p.I1171T | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
ALK I1171T | ganglioneuroblastoma | predicted - sensitive | Ceritinib | Case Reports/Case Series | Actionable | In a clinical case study, Zykadia (ceritinib) treatment resulted in a 43.6% decrease of the primary tumor after 6.5 months of treatment, and complete resolution of metastases at 21 months after initiation of treatment in a pediatric patient with ganglioneuroblastoma harboring ALK I1171T (PMID: 29907598). | 29907598 |