ClinVar Miner

Submissions for variant NM_000038.6(APC):c.3982C>T (p.Gln1328Ter) (rs398123121)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000077990 SCV000226397 pathogenic not provided 2012-10-26 criteria provided, single submitter clinical testing
GeneDx RCV000077990 SCV000567836 pathogenic not provided 2016-03-25 criteria provided, single submitter clinical testing This pathogenic variant is denoted APC c.3982C>T at the cDNA level and p.Gln1328Ter (Q1328X) 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 protein truncation. This variant has been reported in multiple individuals with a history of adenomatous polyposis (Paul 1993, Gismondi 1997, De Rosa 2003) and is considered pathogenic.
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000501536 SCV000591163 pathogenic Familial adenomatous polyposis 2016-10-13 criteria provided, single submitter clinical testing
Invitae RCV000174982 SCV000647486 pathogenic Familial adenomatous polyposis 1 2018-03-28 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the APC gene (p.Gln1328*). While this is not anticipated to result in nonsense mediated decay, it is expected to delete the last 1516 amino acids (~53%) of the APC protein. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals with familial adenomatous polyposis the literature (PMID: 8395941, 9101302, 20685668,26900293, 14961559). ClinVar contains an entry for this variant (Variation ID: 92346). Multiple truncating variants downstream of this truncation have been reported as pathogenic in individuals with FAP (PMID: 17064931). This suggests that deletion of this region of the APC protein is causative of disease. For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV000570934 SCV000667621 pathogenic Hereditary cancer-predisposing syndrome 2016-07-29 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)

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