Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000598959 | SCV000710360 | pathogenic | not provided | 2024-12-17 | criteria provided, single submitter | clinical testing | Frameshift variant predicted to result in protein truncation in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 18199528) |
| Labcorp Genetics |
RCV004568318 | SCV002132256 | pathogenic | Familial adenomatous polyposis 1 | 2024-10-02 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Ala2128Leufs*11) in the APC gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 716 amino acid(s) of the APC protein. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with APC-related conditions. ClinVar contains an entry for this variant (Variation ID: 504055). 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, internal data). 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. |