ClinVar Miner

Submissions for variant NM_000038.6(APC):c.637C>T (p.Arg213Ter) (rs587781392)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000129233 SCV000183988 pathogenic Hereditary cancer-predisposing syndrome 2017-09-01 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
GeneDx RCV000202175 SCV000209567 pathogenic not provided 2018-08-27 criteria provided, single submitter clinical testing This variant is denoted APC c.637C>T at the cDNA level and p.Arg213Ter (R213X) at the protein level. The substitution creates a nonsense variant, which changes an Arginine to a premature stop codon (CGA>TGA), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant has been reported in association with classic and/or attenuated Familial Adenomatous Polyposis (FAP/AFAP) and is considered pathogenic (Miyoshi 1992, Vandrovcová 2004, García-Lozano 2005, Errichiello 2015).
Invitae RCV000227200 SCV000282795 pathogenic Familial adenomatous polyposis 1 2018-04-09 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal at codon 213 (p.Arg213*) of the APC gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in APC are known to be pathogenic. This particular truncation has been reported in the literature in many individuals affected with familial adenomatous polyposis (PMID: 1316610, 20685668, 20223039, 10094547, 17411426), and in an individual affected with colon cancer (PMID: 26681312). For these reasons, this variant has been classified as Pathogenic.
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000502476 SCV000591043 pathogenic Familial adenomatous polyposis 2015-03-04 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000763535 SCV000894348 pathogenic Desmoid disease, hereditary; Carcinoma of colon; Familial adenomatous polyposis 1; Neoplasm of stomach; Hepatocellular carcinoma 2018-10-31 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000825611 SCV000966956 pathogenic Familial multiple polyposis syndrome 2018-04-17 criteria provided, single submitter clinical testing The p.Arg213X variant in APC has been reported in >15 individuals with APC-assoc iated cancers (Miyoshi 1992, Giarola 1999, Stekrova 2006, Friedl 2005, Garcia-L azano 2005, Lagarde 2010, Susswein 2016) and was absent from large population st udies. This variant has been reported as a somatic variant in >90 tumor samples from various cancer types, including colorectal cancer (The Catalogue of Somatic Mutations in Cancer, https://cancer.sanger.ac.uk/cosmic). This variant has also been reported in ClinVar (Variant ID: 140952). This nonsense variant leads to a premature termination codon at position 213, which is predicted to lead to a tr uncated or absent protein. Heterozygous loss of function of the APC gene is an e stablished disease mechanism in individuals with familial adenomatous polyposis (FAP). In summary, this variant meets criteria to be classified as pathogenic fo r FAP in an autosomal dominant manner based upon predicted impact to the protein , presence in affected individuals, and absence in the general population. ACMG/ AMP Criteria applied: PVS1; PS4; PM2.
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic RCV000202175 SCV000257022 pathogenic not provided no assertion criteria provided research

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