ClinVar Miner

Submissions for variant NM_000038.6(APC):c.3785dup (p.Tyr1262Ter)

dbSNP: rs863225345
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000411477 SCV000488589 likely pathogenic Familial adenomatous polyposis 1 2016-05-20 criteria provided, single submitter clinical testing
Invitae RCV000411477 SCV000552541 pathogenic Familial adenomatous polyposis 1 2017-09-25 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. 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. 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). This variant is not present in population databases (ExAC no frequency). 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.
Ambry Genetics RCV001021131 SCV001182708 pathogenic Hereditary cancer-predisposing syndrome 2018-04-19 criteria provided, single submitter clinical testing The c.3785dupA pathogenic mutation, located in coding exon 15 of the APC gene, results from a duplication of A at nucleotide position 3785, causing a translational frameshift with a predicted alternate stop codon (p.Y1262*). This alteration is expected to result in loss of function by premature protein truncation. As such, this alteration is interpreted as a disease-causing mutation.
Myriad Genetics, Inc. RCV000411477 SCV004019745 pathogenic Familial adenomatous polyposis 1 2023-02-15 criteria provided, single submitter clinical testing This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation.
Mayo Clinic Laboratories, Mayo Clinic RCV000202114 SCV000256976 likely pathogenic not provided no assertion criteria provided research

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