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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_004304.4 | chr2:g.29220765G>T | c.3586C>A | p.L1196M | RefSeq | GRCh38/hg38 |
| 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 |
| Clinical Trial | Phase | Therapies | Title | Recruitment Status | Covered Countries | Other Countries |
|---|---|---|---|---|---|---|
| NCT03737994 | Phase II | Cisplatin + Lorlatinib Carboplatin + Lorlatinib Ceritinib Alectinib + Cisplatin Alectinib + Carboplatin Ceritinib + Cisplatin Pemetrexed Disodium Carboplatin + Ceritinib Cisplatin + Ensartinib Carboplatin + Ensartinib Brigatinib + Cisplatin Brigatinib Alectinib Brigatinib + Carboplatin Ensartinib Cisplatin + Pemetrexed Disodium Crizotinib Carboplatin + Pemetrexed Disodium Lorlatinib | Targeted Treatment for ALK Positive Patients Who Have Previously Been Treated for Non-squamous Non-small Cell Lung Cancer | Active, not recruiting | USA | 0 |