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 | |
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, |
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 |