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Gene | ALK |
Variant | L1196M |
Impact List | missense |
Protein Effect | gain of function |
Gene Variant Descriptions | ALK L1196M lies within the protein kinase domain of the Alk protein (UniProt.org). L1196M results in increased Alk kinase activity (PMID: 30258533), modest Alk autophosphorylation, and transformation in cell culture (PMID: 25517749), and confers resistance to Alk inhibitors in the context of ALK rearrangements in culture and in vivo (PMID: 21613408, PMID: 25421750, PMID: 31452835). |
Associated Drug Resistance | Y |
Category Variants Paths |
ALK mutant ALK act mut ALK L1196M ALK mutant ALK L1196X ALK L1196M |
Transcript | NM_004304.5 |
gDNA | chr2:g.29220765G>T |
cDNA | c.3586C>A |
Protein | p.L1196M |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_004304 | chr2:g.29220765G>T | c.3586C>A | p.L1196M | RefSeq | GRCh38/hg38 |
NM_004304.5 | chr2:g.29220765G>T | c.3586C>A | p.L1196M | RefSeq | GRCh38/hg38 |
NM_004304.4 | chr2:g.29220765G>T | c.3586C>A | p.L1196M | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
ALK L1196M | Advanced Solid Tumor | sensitive | Repotrectinib | Preclinical - Cell culture | Actionable | In a preclinical study, Augtyro (repotrectinib) inhibited cell proliferation in transformed cell lines over expressing ALK L1196M in culture (AACR, Cancer Res: April 2016; Volume 57, Abstract #2132). | detail... |
ALK L1196M | neuroblastoma | predicted - sensitive | Ceritinib | Case Reports/Case Series | Actionable | In a Phase I trial, Zykadia (ceritinib) treatment resulted in a partial response with a progression-free survival over 544 days in a pediatric patient with neuroblastoma harboring ALK L1196M (PMID: 34780709; NCT01742286). | 34780709 |
ALK L1196M | Advanced Solid Tumor | predicted - sensitive | TPX-0131 | Preclinical - Biochemical | Actionable | In a preclinical study, TPX-0131 inhibited kinase activity of ALK L1196M in an in vitro assay (PMID: 34158340). | 34158340 |
ALK L1196M | Advanced Solid Tumor | predicted - sensitive | APG-2449 | Preclinical - Biochemical | Actionable | In a preclinical study, APG-2449 inhibited the kinase activity of ALK L1196M in culture (PMID: 35820889). | 35820889 |
ALK L1196M | Advanced Solid Tumor | predicted - sensitive | Conteltinib | Preclinical - Biochemical | Actionable | In a preclinical study, Conteltinib (CT-707) inhibited ALK L1196M activity in an in vitro assay (PMID: 36424628). | 36424628 |