ClinVar Miner

Submissions for variant NM_000038.6(APC):c.476dup (p.Tyr159Ter) (rs878853451)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000229992 SCV000282764 pathogenic Familial adenomatous polyposis 1 2018-05-01 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Tyr159*) 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 the literature in an individual with familial adenomatous polyposis (FAP) (PMID: 20685668). In addition, a different nucleotide change (c.477C>G) which also results in a premature stop signal at codon 159 (p.Tyr159*) has also been reported in individuals with FAP (PMID: 20223039, 8956059). ClinVar contains an entry for this variant (Variation ID: 236607). Loss-of-function variants in APC are known to be pathogenic (PMID: 17963004, 20685668). For these reasons, this variant has been classified as Pathogenic.
Counsyl RCV000229992 SCV000488330 likely pathogenic Familial adenomatous polyposis 1 2016-03-01 criteria provided, single submitter clinical testing
GeneDx RCV000486696 SCV000564559 pathogenic not provided 2015-02-06 criteria provided, single submitter clinical testing This duplication of one nucleotide is denoted APC c.476dupA at the cDNA level and p.Tyr159Ter (Y159X) at the protein level. The normal sequence, with the base that is duplicated in braces, is TATT[A]CGCT. The duplication creates a nonsense variant, which changes a Tyrosine to a premature stop codon. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. APC Tyr159Ter has been reported in association with colonic adenomatous polyposis (Lagarde 2013). This variant is considered pathogenic.

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