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Gene ALK
Variant F1245C
Impact List missense
Protein Effect gain of function
Gene Variant Descriptions ALK F1245C lies within the protein kinase domain of the Alk protein (UniProt.org). F1245C results in increased downstream signaling and is transforming in cell culture (PMID: 21838707, PMID: 25517749).
Associated Drug Resistance Y
Category Variants Paths

ALK mutant ALK F1245X ALK F1245C

ALK mutant ALK act mut ALK F1245C

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Transcript NM_004304.5
gDNA chr2:g.29213993A>C
cDNA c.3734T>G
Protein p.F1245C
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
NM_004304 chr2:g.29213993A>C c.3734T>G p.F1245C RefSeq GRCh38/hg38
NM_004304.4 chr2:g.29213993A>C c.3734T>G p.F1245C RefSeq GRCh38/hg38
NM_004304.5 chr2:g.29213993A>C c.3734T>G p.F1245C RefSeq GRCh38/hg38

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
ALK F1245C Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, a transformed cell line expressing ALK F1245C was sensitive to Alunbrig (brigatinib) in culture, resulting in cell growth inhibition (PMID: 27049722). 27049722
ALK F1245C neuroblastoma resistant Crizotinib Preclinical - Pdx & cell culture Actionable In a preclinical study, Xalkori (crizotinib) did not inhibit growth of neuroblastoma cells over expressing ALK F1245C in culture, and only delayed tumor growth in patient-derived xenograft models harboring ALK F1245C (PMID: 26554404). 26554404
ALK F1245C neuroblastoma sensitive Lorlatinib Preclinical - Pdx & cell culture Actionable In a preclinical study, Lorlatinib (PF-06463922) inhibited growth of neuroblastoma cells over expressing ALK F1245C in culture, and induced rapid and sustained complete tumor regression in patient-derived xenograft models harboring ALK F1245C (PMID: 26554404). 26554404
ALK F1245C Advanced Solid Tumor sensitive Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, Lorlatinib (PF-06463922) inhibited foci formation more efficiently than Xalkori (crizotinib) in transformed cells over expressing ALK F1245C in culture (PMID: 26554404). 26554404
ALK F1245C Advanced Solid Tumor predicted - sensitive TPX-0131 Preclinical - Biochemical Actionable In a preclinical study, TPX-0131 inhibited kinase activity of ALK F1245C in an in vitro assay (PMID: 34158340). 34158340
ALK F1245C Advanced Solid Tumor sensitive Repotrectinib Preclinical - Cell culture Actionable In a preclinical study, Augtyro (repotrectinib) decreased Alk phosphorylation and neurite outgrowth in cells expressing ALK F1245C in culture (PMID: 31852910). 31852910
ALK F1245C neuroblastoma sensitive Ceritinib + Ribociclib Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of Zykadia (ceritinib) and Kisqali (ribociclib) inhibited proliferation in a neuroblastoma cell line harboring ALK F1245C in culture, and resulted in enhanced tumor growth inhibition compared to either Zykadia (ceritinib) or Kisqali (ribociclib) alone (P=0.04 and P<0.0001, respectively) and induced complete and sustained tumor regression in a patient-derived xenograft (PDX) model (PMID: 27986745). 27986745