Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV003537287 | SCV000960530 | pathogenic | Familial adenomatous polyposis 1 | 2018-09-04 | criteria provided, single submitter | clinical testing | A different truncation (p.Glu1538Ilefs*5) that lies downstream of this variant has been determined to be pathogenic (PMID: 8162051, 20223039, 20513532, 20685668, 21643010, 21779980). This suggests that deletion of this region of the APC protein is causative of disease. This variant has not been reported in the literature in individuals with APC-related disease. 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.Leu1506*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 1338 amino acids of the APC protein. For these reasons, this variant has been classified as Pathogenic. This variant is expected to disrupt the EB1 and HDLG binding sites, which mediate interactions with the cytoskeleton (PMID: 15311282, 17293347). While functional studies have not been performed to directly test the effect on APC protein function, this suggests that disruption of the C-terminal portion of the protein is functionally important. |