Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| ARUP Laboratories, |
RCV000756997 | SCV000885016 | pathogenic | not provided | 2018-06-04 | criteria provided, single submitter | clinical testing | The APC c.2589C>A; p.Tyr863Ter variant, to our knowledge, is not reported in the medical literature or gene specific databases. However, a different nucleotide alteration causing the same protein effect (c.2589C>G; p.Tyr863Ter) is reported in an individual with familial adenomatous polyposis (Friedl 2005). The p.Tyr863Ter variant is absent from the general population databases (1000 Genomes Project, Exome Variant Server, and Genome Aggregation Database), indicating it is not a common polymorphism. This variant induces an early termination codon and is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Based on available information, this variant is considered to be pathogenic. REFERENCES Friedl W et al. Familial adenomatous polyposis: experience from a study of 1164 unrelated german polyposis patients. Hered Cancer Clin Pract. 2005 Sep 15;3(3):95-114. |
| Invitae | RCV003768273 | SCV001592223 | pathogenic | Familial adenomatous polyposis 1 | 2020-02-29 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. 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. 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. This variant has not been reported in the literature in individuals with APC-related conditions. ClinVar contains an entry for this variant (Variation ID: 618529). 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.Tyr863*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 1981 amino acids of the APC protein. |