Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV004563872 | SCV001582979 | pathogenic | Familial adenomatous polyposis 1 | 2021-07-09 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (ExAC no frequency). For these reasons, this variant has been classified as Pathogenic. This variant is expected to delete a large portion of the C-terminal region of the APC protein, including the Basic Domain, the EB1 Binding Site, and the HDLG Binding Site, which mediate interactions with the cytoskeleton (PMID: 15311282, 17293347). Although functional studies have not been performed for this variant, different truncating variants (p.Ser1276* and p.Arg1450*) that lie downstream of this variant have been determined to be pathogenic (PMID: 9452101, 15108286, 8103406, 8730280, 8990002). This suggests that deletion of this region of the APC protein is causative of disease. This variant has been observed in an individual affected with familial adenomatous polyposis (PMID: 20513532). This sequence change results in a premature translational stop signal in the APC gene (p.Gln1237*). While this is not anticipated to result in nonsense mediated decay, it is expected to delete the last 1607 amino acids of the APC protein. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV001800993 | SCV002046948 | pathogenic | not specified | 2021-04-20 | criteria provided, single submitter | clinical testing | This nonsense variant causes the premature termination of APC protein synthesis. In addition, it has been reported in an individual affected with familial adenomatous polyposis (FAP) in the published literature (PMID: 20513532 (2010) and 27158207 (2016)). This variant has not been reported in large, multi-ethnic general populations. Therefore, the variant is classified as pathogenic. |