Missing content? – Request curation!
Request curation for specific Genes, variants, or PubMed publications.
Have questions, comments or suggestions? - Let us know!
Email us at : ckbsupport@jax.org
Gene | ALK |
Variant | L1196Q |
Impact List | missense |
Protein Effect | unknown |
Gene Variant Descriptions | ALK L1196Q lies within the protein kinase domain of the Alk protein (UniProt.org). L1196Q has been demonstrated to confer resistance to Alk inhibitors in the context of ALK rearrangements (PMID: 23239810, PMID: 25749034, PMID: 33209633), but has not been biochemically characterized and therefore, its effect on Alk protein function is unknown (PubMed, Jul 2022). |
Associated Drug Resistance | Y |
Transcript | NM_004304.4 |
gDNA | chr2:g.29220764A>T |
cDNA | c.3587T>A |
Protein | p.L1196Q |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_004304.4 | chr2:g.29220764A>T | c.3587T>A | p.L1196Q | RefSeq | GRCh38/hg38 |
NM_004304 | chr2:g.29220764A>T | c.3587T>A | p.L1196Q | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
EML4 - ALK ALK L1196Q | Advanced Solid Tumor | resistant | Entrectinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196Q were resistant to Rozlytrek (entrectinib) in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK L1196Q | Advanced Solid Tumor | sensitive | Ceritinib | Preclinical - Cell culture | Actionable | In a preclinical study, Zykadia (ceritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK L1196Q in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK L1196Q | Advanced Solid Tumor | sensitive | Gilteritinib | Preclinical - Cell culture | Actionable | In a preclinical study, Xospata (gilteritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK L1196Q in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK L1196Q | lung non-small cell carcinoma | predicted - sensitive | Brigatinib | Case Reports/Case Series | Actionable | In a clinical case study, Alunbrig (brigatinib) treatment resulted in a partial response in a patient with metastatic lung adenocarcinoma harboring EML4-ALK and an acquired ALK L1196Q who progressed on prior Alecensa (alectinib) treatment, the response was ongoing after 17 months of treatment (PMID: 33209633). | 33209633 |
EML4 - ALK ALK L1196Q | Advanced Solid Tumor | resistant | Alectinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196Q demonstrated resistance to Alecensa (alectinib) in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK L1196Q | Advanced Solid Tumor | sensitive | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Lorbrena (lorlatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK L1196Q in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK L1196Q | Advanced Solid Tumor | sensitive | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK L1196Q in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK L1196Q | lung non-small cell carcinoma | predicted - resistant | Alectinib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with metastatic lung adenocarcinoma harboring EML4-ALK demonstrated disease progression following a 15-month partial response to Alecensa (alectinib) treatment, and was found to have acquired ALK L1196Q (PMID: 33209633). | 33209633 |
EML4 - ALK ALK L1196Q | Advanced Solid Tumor | resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196Q were resistant to Xalkori (crizotinib) in culture (PMID: 33627640). | 33627640 |
Molecular Profile | Protein Effect | Treatment Approaches |
---|---|---|
ALK L1196Q | unknown | ALK Inhibitor |
EML4 - ALK ALK L1196Q |