ClinVar Miner

Submissions for variant NM_000038.6(APC):c.1213C>T (p.Arg405Ter) (rs587779780)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000202096 SCV000148975 pathogenic not provided 2016-08-14 criteria provided, single submitter clinical testing This pathogenic variant is denoted APC c.1213C>T at the cDNA level and p.Arg405Ter (R405X) at the protein level. The substitution creates a nonsense variant, changing an Arginine to a premature stop codon (CGA>TGA). This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. APC Arg405Ter has been observed in association with Familial Adenomatous Polyposis (Nagase 1992, Friedl 2005, Lagarde 2010). We therefore consider this variant to be pathogenic.
Ambry Genetics RCV000115066 SCV000186398 pathogenic Hereditary cancer-predisposing syndrome 2017-01-13 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)
Invitae RCV000234357 SCV000282691 pathogenic Familial adenomatous polyposis 1 2018-12-11 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg405*) 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 observed in individuals affected with familial adenomatous polyposis (PMID: 1338764, 20685668, 20223039). ClinVar contains an entry for this variant (Variation ID: 127275). Loss-of-function variants in APC are known to be pathogenic (PMID: 20685668, 17963004). For these reasons, this variant has been classified as Pathogenic.
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000500146 SCV000591065 pathogenic Familial adenomatous polyposis criteria provided, single submitter clinical testing
HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology RCV000234357 SCV000803187 pathogenic Familial adenomatous polyposis 1 2018-06-26 criteria provided, single submitter research
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000202096 SCV000885014 pathogenic not provided 2017-06-29 criteria provided, single submitter clinical testing The APC c.1213C>T; p.Arg405Ter variant (rs587779780) has been reported in multiple individuals with familial adenomatous polyposis (Friedl 2005, Nagase 1992). It is listed as pathogenic in ClinVar (Variation ID: 127275), and not observed in the general population databases (1000 Genomes Project, Exome Variant Server, and Genome Aggregation Database), indicating it is not a common polymorphism. The variant introduces a premature termination codon, and is predicted to result in a truncated protein or an absent transcript. Based on the above information, this variant is considered pathogenic. References: Friedl W et al. Familial adenomatous polyposis: experience from a study of 1164 unrelated german polyposis patients. Hered Cancer Clin Pract. 2005; 3(3):95-114. Nagase H et al. Screening for germ-line mutations in familial adenomatous polyposis patients: 61 new patients and a summary of 150 unrelated patients. Hum Mutat. 1992; 1(6):467-73.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000202096 SCV000887502 pathogenic not provided 2017-11-16 criteria provided, single submitter clinical testing
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic RCV000202096 SCV000256910 pathogenic not provided no assertion criteria provided clinical testing

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