ClinVar Miner

Submissions for variant NM_000038.6(APC):c.3786T>G (p.Tyr1262Ter) (rs147411334)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000646268 SCV000768036 pathogenic Familial adenomatous polyposis 1 2017-09-29 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the APC gene (p.Tyr1262*). While this is not anticipated to result in nonsense mediated decay, it is expected to delete the last 1582 amino acids of the APC protein. This variant is not present in population databases (ExAC no frequency). While this variant has not been reported in the literature in APC-related diseases, loss-of-function variants in APC are known to be pathogenic (PMID: 17963004, 20685668). Different variants (c.3786T>A and c.3785dupA) giving rise to the same protein effect observed here (p.Tyr1262*) have been reported as pathogenic in individuals affected with familial adenomatous polyposis (PMID: 11247896, Invitae). In addition, a different truncation downstream of this variant (p.Ser1276*) has been determined to be pathogenic (PMID: 9452101, 10094547, 15108286, Invitae). 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.

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