Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV004562094 | SCV001416274 | pathogenic | Familial adenomatous polyposis 1 | 2020-05-20 | criteria provided, single submitter | clinical testing | This sequence change results in a premature translational stop signal in the APC gene (p.Tyr737*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 2107 amino acids of the APC protein. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with APC-related conditions. 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. A different truncation (p.Tyr2645Lysfs*14) that lies downstream of this variant has been determined to be pathogenic (PMID: 9824584, 1316610, 27081525, 8381579, 22135120, 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. |
| Myriad Genetics, |
RCV004562094 | SCV004045628 | pathogenic | Familial adenomatous polyposis 1 | 2023-05-04 | 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. |
| All of Us Research Program, |
RCV004004896 | SCV004822014 | pathogenic | Classic or attenuated familial adenomatous polyposis | 2023-07-10 | criteria provided, single submitter | clinical testing | This variant changes 1 nucleotide in exon 16 of the APC gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. To our knowledge, this variant has been reported in two sister affected with papillary thyroid carcinoma (PTC) and familial adenomatous polyposis (FAP) (PMID: 29696324). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of APC function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic. |