ClinVar Miner

Submissions for variant NM_000038.6(APC):c.5585dup (p.Leu1862fs) (rs1554086823)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000605702 SCV000712849 likely pathogenic Familial multiple polyposis syndrome 2020-02-06 criteria provided, single submitter clinical testing The p.Leu1862PhefsX7 variant in APC has not been previously reported in individuals with familial adenomatous polyposis (FAP) and was absent from large population studies. This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 1862 and leads to a premature termination codon 7 amino acids downstream. This termination codon occurs within the last exon and is, therefore, likely to escape nonsense mediated decay (NMD) and result in a truncated protein. Truncating variants in the last exon of APC, including multiple variants downstream of this variant, have been reported in individuals with FAP. In summary, although additional studies are required to fully establish its clinical significance, the p.Arg2237X variant is classified as likely pathogenic for FAP in an autosomal dominant manner. ACMG/AMP Criteria applied: PVS1_Strong, PM2.

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