ClinVar Miner

Submissions for variant NM_000038.6(APC):c.1660C>T (p.Arg554Ter) (rs137854573)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000129303 SCV000184065 pathogenic Hereditary cancer-predisposing syndrome 2018-03-28 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)
University of Washington Department of Laboratory Medicine,University of Washington RCV000210172 SCV000266005 pathogenic Colorectal cancer, susceptibility to 2015-11-20 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000844608 SCV000271308 pathogenic Familial multiple polyposis syndrome 2019-01-17 criteria provided, single submitter clinical testing The p.Arg554X variant in APC has been previously reported in at least 15 individ uals with familial adenomatous polyposis (FAP) (Fodde 1992, Ripa 2002, Friedl 20 05, Rivera 2011, Bisgaard 2004, Truta 2005) and was absent from large population studies. It has also been reported in ClinVar (Variation ID#807). This nonsense variant leads to a premature termination codon at position 554, which is predic ted to lead to a truncated or absent protein. Heterozygous loss of function of t he APC gene is an established disease mechanism in individuals with FAP. In summ ary, this variant meets criteria to be classified as pathogenic for familial ade nomatous polyposis in an autosomal dominant manner. ACMG/AMP Criteria applied: P VS1, PS4, PM2.
GeneDx RCV000482405 SCV000567480 pathogenic not provided 2018-04-06 criteria provided, single submitter clinical testing This variant is denoted APC c.1660C>T at the cDNA level and p.Arg554Ter (R554X) 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 Familial Adenomatous Polyposis (FAP) (Fodde 1992, van der Luijt 1997, Blaker 2003, Friedl and Aretz 2005, Castellsague 2010) and is considered pathogenic.
Invitae RCV000000845 SCV000647193 pathogenic Familial adenomatous polyposis 1 2018-08-24 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg554*) in the APC gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported in numerous individuals affected with familial adenomatous polyposis (PMID: 1324223, 20685668, 15108286, 15951963, 20924072, 12357334, 20223039). ClinVar contains an entry for this variant (Variation ID: 807). Loss-of-function variants in APC are known to be pathogenic (PMID: 20685668, 17963004). For these reasons, this variant has been classified as Pathogenic.
Color RCV000129303 SCV000686849 pathogenic Hereditary cancer-predisposing syndrome 2017-08-20 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000763541 SCV000894354 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
OMIM RCV000000845 SCV000020995 pathogenic Familial adenomatous polyposis 1 1992-08-01 no assertion criteria provided literature only
Yale Center for Mendelian Genomics,Yale University RCV000000845 SCV000784633 pathogenic Familial adenomatous polyposis 1 2015-11-27 no assertion criteria provided literature only

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