Total submissions: 5
| 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 | |
| Labcorp Genetics |
RCV000411477 | SCV000552541 | pathogenic | Familial adenomatous polyposis 1 | 2017-09-25 | 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. |
| 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, |
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, |
RCV000202114 | SCV000256976 | likely pathogenic | not provided | no assertion criteria provided | research |