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Gene | ALK |
Variant | L1196P |
Impact List | missense |
Protein Effect | gain of function - predicted |
Gene Variant Descriptions | ALK L1196P lies within the protein kinase domain of the Alk protein (UniProt.org). L1196P results in both increased phosphorylation of Alk and proliferation, and has been demonstrated to confer resistance to Alk inhibitors in the context of EML4-ALK in culture (PMID: 38448512), and therefore, is predicted to lead to a gain of Alk protein function. |
Associated Drug Resistance | Y |
Category Variants Paths |
ALK mutant ALK act mut ALK L1196P ALK mutant ALK L1196X ALK L1196P |
Transcript | NM_004304.5 |
gDNA | chr2:g.29220764A>G |
cDNA | c.3587T>C |
Protein | p.L1196P |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_004304.5 | chr2:g.29220764A>G | c.3587T>C | p.L1196P | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
EML4 - ALK ALK L1196P | lung non-small cell carcinoma | predicted - resistant | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical case study, ALK L1196P was identified in the post-progression circulating tumor DNA of a patient with relapsed non-small cell lung cancer harboring EML4-ALK treated with Lorbrena (lorlatinib), and in a preclinical study, cells expressing EML4-ALK and ALK L1196P were resistant to Lorbrena (lorlatinib) in culture (PMID: 38448512). | 38448512 |
EML4 - ALK ALK L1196P | Advanced Solid Tumor | resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, cells expressing EML4-ALK and ALK L1196P were resistant to Xalcori (crizotinib) in culture (PMID: 38448512). | 38448512 |
EML4 - ALK ALK L1196P | Advanced Solid Tumor | resistant | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, cells expressing EML4-ALK and ALK L1196P were resistant to Alunbrig (brigatinib) in culture (PMID: 38448512). | 38448512 |
EML4 - ALK ALK L1196P | Advanced Solid Tumor | resistant | Ceritinib | Preclinical - Cell culture | Actionable | In a preclinical study, cells expressing EML4-ALK and ALK L1196P were resistant to Zykadia (ceritinib) in culture (PMID: 38448512). | 38448512 |
EML4 - ALK ALK L1196P | Advanced Solid Tumor | resistant | Alectinib | Preclinical - Cell culture | Actionable | In a preclinical study, cells expressing EML4-ALK and ALK L1196P were resistant to Alecensa (alectinib) in culture (PMID: 38448512). | 38448512 |
EML4 - ALK ALK L1196P | Advanced Solid Tumor | resistant | TPX-0131 | Preclinical - Cell culture | Actionable | In a preclinical study, cells expressing EML4-ALK and ALK L1196P were resistant to TPX-0131 in culture (PMID: 38448512). | 38448512 |
EML4 - ALK ALK L1196P | Advanced Solid Tumor | resistant | Repotrectinib | Preclinical - Cell culture | Actionable | In a preclinical study, cells expressing EML4-ALK and ALK L1196P were resistant to Augtyro (repotrectinib) in culture (PMID: 38448512). | 38448512 |