Gene Variant Detail

Gene ALK
Variant L1196M
Impact List missense
Protein Effect gain of function - predicted
Gene Variant Descriptions ALK L1196M lies within the protein kinase domain of the Alk protein (UniProt.org). L1196M is predicted to confer a gain of function to the Alk protein as demonstrated by transformation activity and modest autophosphorylation of Alk in culture (PMID: 25517749), and confers resistance to Alk inhibitors in the context of ALK rearrangements in culture (PMID: 21613408, PMID: 25421750).
Associated Drug Resistance Y

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Transcript NM_004304
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

Filtering

  • Case insensitive filtering will display rows where any text in any cell matches the filter term
  • Simple literal full or partial string matches
  • Separate multiple filter terms with a spaces, order doesn't matter (a b c and c b a are equivalent )
  • Filtering will only apply to rows that are already loaded on the page, filtering has no impact on query parameters
  • Use quotes to match a longer phrase which contains spaces "mtor c1483f"

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
EML4-ALK ALK L1196M ALK F1174V Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK F1174V was identified as a compound mutation in transformed cells expressing ALK L1196M in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). 29650534
ALK rearrange ALK G1202R ALK L1196M non-small cell lung carcinoma resistant Lorlatinib Clinical Study Actionable In a clinical study, ALK L1196M was identified as an acquired mutation in an ALK-positive non-small cell lung cancer patient harboring ALK G1202R who developed resistance to Lorlatinib (PF-06463922) after initial response (PMID: 29650534). 29650534
NPM1-ALK ALK L1196M Advanced Solid Tumor sensitive Ceritinib Preclinical - Cell culture Actionable In a preclinical trial, Zykadia (ceritinib) inhibited growth of transformed cells expressing NPM1-ALK with ALK L1196M in culture (PMID: 25421750). 25421750
NPM1-ALK ALK L1196M Advanced Solid Tumor resistant ASP3026 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK L1196M were resistant to ASP3026 treatment in culture (PMID: 25421750). 25421750
NPM1-ALK ALK L1196M Advanced Solid Tumor decreased response Alectinib Preclinical - Cell culture Actionable In a preclinical trial, Alecensa (alectinib) inhibited growth of transformed cells expressing NPM1-ALK with ALK L1196M to a lesser degree than cells expressing NPM1-ALK in culture (PMID: 25421750). 25421750
NPM1-ALK ALK L1196M Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing NPM1-ALK with ALK L1196M in culture (PMID: 25421750). 25421750
NPM1-ALK ALK L1196M Advanced Solid Tumor decreased response Crizotinib Preclinical - Cell culture Actionable In a preclinical trial, Xalkori (crizotinib) inhibited growth of transformed cells expressing NPM1-ALK with ALK L1196M to a lesser degree than cells expressing NPM1-ALK in culture (PMID: 25421750). 25421750
EML4-ALK ALK L1196M ALK G1202R Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK L1196M was identified as a compound mutation in transformed cells expressing ALK G1202R in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). 29650534
EML4-ALK ALK L1196M ALK F1174C Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK F1174C was identified as a compound mutation in transformed cells expressing ALK L1196M in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). 29650534
EML4-ALK ALK C1156Y ALK L1196M Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK L1196M was identified as a compound mutation in transformed cells expressing ALK C1156Y in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). 29650534
EML4-ALK ALK C1156Y ALK L1196M lung adenocarcinoma resistant Crizotinib Clinical Study Actionable In a clinical case study, a patient with lung adenocarcinoma harboring EML4-ALK achieved a partial response when treated with Xalkori (crizotinib), however, after 5 months, the patient progressed and was found to harbor secondary resistance mutations, ALK C1156Y and ALK L1196M (PMID: 20979473). 20979473
NPM1-ALK ALK L1122V ALK L1196M Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK L1122V and ALK L1196M were resistant to Xalkori (crizotinib) treatment in culture (PMID: 25421750). 25421750
NPM1-ALK ALK L1122V ALK L1196M anaplastic large cell lymphoma resistant Brigatinib Preclinical - Cell culture Actionable In a preclinical study, anaplastic large cell lymphoma cell lines harboring NPM1-ALK with ALK L1122V and ALK L1196M were resistant to Alunbrig (brigatinib) in culture (PMID: 25421750). 25421750
NPM1-ALK ALK L1122V ALK L1196M Advanced Solid Tumor resistant ASP3026 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK L1122V and ALK L1196M were resistant to ASP3026 treatment in culture (PMID: 25421750). 25421750
NPM1-ALK ALK L1122V ALK L1196M Advanced Solid Tumor resistant Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK L1122V and ALK L1196M were resistant to Alunbrig (brigatinib) treatment in culture (PMID: 25421750). 25421750
NPM1-ALK ALK L1122V ALK L1196M Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK L1122V and ALK L1196M were resistant to Alecensa (alectinib) treatment in culture (PMID: 25421750). 25421750
ALK rearrange ALK L1196M non-small cell lung carcinoma resistant Crizotinib Clinical Study Actionable In a clinical case study, four non-small cell lung carcinoma patients harboring an ALK rearrangement responded to Xalkori (crizotinib) therapy, but then progressed, and was found to have acquired ALK L1196M (PMID: 25724526). 25724526
ALK rearrange ALK L1196M non-small cell lung carcinoma resistant Crizotinib Clinical Study Actionable In a clinical case study, ALK L1196M was identified in biopsies from a non-small cell lung cancer patient harboring ALK rearrangement who developed resistance to Xalkori (crizotinib) (PMID: 22277784). 22277784
EML4-ALK ALK G1269A ALK L1196M Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK L1196M was identified as a compound mutation in transformed cells expressing ALK G1269A in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). 29650534
EML4-ALK ALK G1269A ALK L1196M non-small cell lung carcinoma resistant Crizotinib Clinical Study Actionable In a clinical case study, a patient with non-small cell lung carcinoma harboring EML4-ALK demonstrated a partial response when treated with Xalkori (crizotinib), however, after 6 months the patient progressed and was found to harbor two secondary resistance mutations, ALK G1269A and ALK L1196M (PMID: 23344087). 23344087
EML4-ALK ALK L1196M ALK F1174L Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK F1174L was identified as a compound mutation in transformed cells expressing ALK L1196M in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). 29650534
EML4-ALK ALK L1196M ALK L1198F Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and ALK L1198F displayed enhanced resistance to growth inhibition mediated by Lorlatinib (PF-06463922) in culture (PMID: 26698910). 26698910
EML4-ALK ALK L1196M ALK L1198F Advanced Solid Tumor resistant Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and ALK L1198F were resistant to growth inhibition mediated by Alunbrig (brigatinib) in culture (PMID: 26698910). 26698910
EML4-ALK ALK L1196M ALK L1198F Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, introduction of an additional ALK mutation L1198F in transformed cells expressing ALK L1196M in the context of EML4-ALK reduced resistance to Xalkori (crizotinib) mediated growth inhibition in culture (PMID: 26698910). 26698910
EML4-ALK ALK L1196M ALK L1198F Advanced Solid Tumor resistant Ceritinib Preclinical Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and ALK L1198F displayed enhanced resistance to growth inhibition mediated by Zykadia (ceritinib) in culture (PMID: 26698910). 26698910
EML4-ALK ALK L1196M ALK L1198F Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and ALK L1198F displayed enhanced resistance to growth inhibition mediated by Alecensa (alectinib) in culture (PMID: 26698910). 26698910
ALK rearrange ALK V1180L ALK L1196M ALK G1202R non-small cell lung carcinoma predicted - resistant Brigatinib Clinical Study Actionable In a clinical case study, ALK G1202R and ALK L1196M were identified at disease progression while on Alunbrig (brigatinib) treatment in liquid biopsy of a patient with ALK-positive non-small cell lung cancer also harboring an ALK V1180L (PMID: 29935304). 29935304
EML4-ALK ALK L1196M Advanced Solid Tumor sensitive Repotrectinib Preclinical - Cell culture Actionable In a preclinical study, Repotrectinib (TPX-0005) inhibited Alk activity and proliferation of transformed cells over expressing ALK L1196M in the context of EML4-ALK in culture (European Journal of Cancer , Volume 69, S32). detail...
EML4-ALK ALK L1196M Advanced Solid Tumor sensitive Ensartinib Preclinical Actionable In a preclinical study, Ensartinib (X-396) inhibited growth and Alk phosphorylation in cells expressing the Xalkori (crizotinib) resistance mutation, EML4-ALK ALK L1196M (PMID: 21613408). 21613408
EML4-ALK ALK L1196M Advanced Solid Tumor sensitive Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK L1196M demonstrated sensitivity to treatment with Zykadia (ceritinib) in culture (PMID: 27432227). 27432227
EML4-ALK ALK L1196M Advanced Solid Tumor sensitive Ceritinib Preclinical - Cell culture Actionable In a preclinical study, Zykadia (ceritinib) inhibited growth of transformed cells expressing EML4-ALK with ALK L1196M in culture (PMID: 26698910) 26698910
EML4-ALK ALK L1196M Advanced Solid Tumor conflicting Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M were resistant to growth inhibition mediated by Lorlatinib (PF-06463922) in culture (PMID: 26698910), however, in another study, comparable cells demonstrated sensitivity in culture (PMID: 27432227). 26698910 27432227
EML4-ALK ALK L1196M Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK L1196M in the context of EML4-ALK were resistant to Xalkori (crizotinib) in culture (PMID: 22277784). 22277784
EML4-ALK ALK L1196M Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK L1196M in the context of EML4-ALK were insensitive to Xalkori (crizotinib) as demonstrated by a lack of growth inhibition and Alk phosphorylation in culture (PMID: 26698910). 26698910
EML4-ALK ALK L1196M Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell line xenograft Actionable In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing ALK L196M in the context of EML4-ALK in culture and reduced tumor growth in cell line xenograft models (PMID: 27780853). 27780853
EML4-ALK ALK L1196M Advanced Solid Tumor conflicting Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M demonstrated decreased sensitivity to Alecensa (alectinib) compared to cells expressing EML4-ALK with wild-type ALK, in culture (PMID: 26698910). 26698910
EML4-ALK ALK L1196M Advanced Solid Tumor conflicting Alectinib Preclinical - Cell line xenograft Actionable In a preclinical study, Alecensa (alectinib) inhibited growth of transformed cells expressing an EML4-ALK fusion and ALK L1196M in culture and in cell line xenograft models (PMID: 21575866). 21575866
EML4-ALK ALK L1196M Advanced Solid Tumor sensitive Entrectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M were sensitive to Entrectinib (RXDX-101), resulting in anti-proliferative activity in culture (PMID: 26939704). 26939704
EML4-ALK ALK L1196M non-small cell lung carcinoma sensitive Ceritinib Preclinical - Cell line xenograft Actionable In a preclinical study, Zykadia (ceritinib) inhibited cell survival and PI3K/AKT, MEK/ERK, and mTOR signaling in two human non-small cell lung carcinoma cell lines harboring the Xalkori (crizotinib) resistance mutation EML4-ALK ALK L1196M in culture and inhibited tumor growth in xenograft models of one of those cell lines (PMID: 24675041). 24675041
EML4-ALK ALK L1196M non-small cell lung carcinoma sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited growth of non-small cell lung cancer cells expressing ALK L1196M in the context of EML4-ALK in culture (PMID: 21502504). 21502504
EML4-ALK ALK L1196M non-small cell lung carcinoma sensitive Lorlatinib Preclinical - Cell line xenograft Actionable In a preclinical study, Lorlatinib (PF-06463922) inhibited Alk phosphorylation and proliferation of non-small cell lung carcinoma cells over expressing ALK L1196M in the context of EML4-ALK in culture, and resulted in tumor regression in cell line xenograft models (PMID: 26144315). 26144315
EML4-ALK ALK L1196M ALK L1256F Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK L1256F was identified as a compound mutation in transformed cells expressing ALK L1196M in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). 29650534
ALK L1196M Advanced Solid Tumor sensitive Repotrectinib Preclinical - Cell culture Actionable In a preclinical study, Repotrectinib (TPX-0005) inhibited cell proliferation in transformed cell lines over expressing ALK L1196M in culture (AACR, Cancer Res: April 2016; Volume 57, Abstract #2132). detail...
NPM1-ALK ALK L1196M ALK D1203N Advanced Solid Tumor decreased response Ceritinib Preclinical - Cell culture Actionable In a preclinical study, Zykadia (ceritinib) inhibited growth of transformed cells expressing NPM1-ALK with ALK L1196M and ALK D1203N to a lesser degree than cells expressing NPM1-ALK in culture (PMID: 25421750). 25421750
NPM1-ALK ALK L1196M ALK D1203N Advanced Solid Tumor sensitive ASP3026 Preclinical - Cell culture Actionable In a preclinical study, ASP3026 inhibited growth of transformed cells expressing NPM1-ALK with ALK L1196M and ALK D1203N in culture (PMID: 25421750). 25421750
NPM1-ALK ALK L1196M ALK D1203N Advanced Solid Tumor resistant Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK L1196M and ALK D1203N were resistant to Alunbrig (brigatinib) treatment in culture (PMID: 25421750). 25421750
NPM1-ALK ALK L1196M ALK D1203N Advanced Solid Tumor decreased response Alectinib Preclinical - Cell culture Actionable In a preclinical trial, Alecensa (alectinib) inhibited growth of transformed cells expressing NPM1-ALK with ALK L1196M and ALK D1203N to a lesser degree than cells expressing NPM1-ALK in culture (PMID: 25421750). 25421750
NPM1-ALK ALK L1196M ALK D1203N Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NPM1-ALK with ALK L1196M and ALK D1203N were resistant to Xalkori (crizotinib) treatment in culture (PMID: 25421750). 25421750
EML4-ALK ALK L1196M ALK I1171S Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK I1171S was identified as a compound mutation in transformed cells expressing ALK L1196M in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). 29650534
EML4-ALK ALK L1196M ALK I1179V Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK I1179V was identified as a compound mutation in transformed cells expressing ALK L1196M in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). 29650534