ClinVar Miner

Submissions for variant NM_000038.6(APC):c.487C>T (p.Gln163Ter) (rs863225362)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000500940 SCV000591034 pathogenic Familial adenomatous polyposis 2013-09-26 criteria provided, single submitter clinical testing
Invitae RCV000548404 SCV000647543 pathogenic Familial adenomatous polyposis 1 2018-11-30 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal at codon 163 (p.Gln163*) 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 variant has been reported in the literature in a family affected with colonic adenomas and colorectal cancer (PMID: 9585611). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV000202083 SCV000779341 pathogenic not provided 2017-11-08 criteria provided, single submitter clinical testing This variant is denoted APC c.487C>T at the cDNA level and p.Gln163Ter (Q163X) at the protein level. The substitution creates a nonsense variant, which changes a Glutamine to a premature stop codon (CAG>TAG), 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 several patients with adenomatous polyposis (Soravia 1998, Sieber 2006, Kerr 2013) and is considered pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000500940 SCV000916510 pathogenic Familial adenomatous polyposis 2018-10-22 criteria provided, single submitter clinical testing Variant summary: APC c.487C>T (p.Gln163X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (eg. p.Arg332X, p.Gly721fsX3, p.Asp849fsX11). The variant was absent in 237506 control chromosomes. c.487C>T has been reported in the literature in multiple individuals affected with Familial Adenomatous Polyposis (Scott_2001, Sieber_2006, Soravia_1998). These data indicate that the variant is very likely to be associated with disease. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic RCV000202083 SCV000257007 pathogenic not provided no assertion criteria provided clinical testing

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