Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV003772884 | SCV002211514 | pathogenic | Familial adenomatous polyposis 1 | 2020-11-17 | criteria provided, single submitter | clinical testing | 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. 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. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Glu2035Lysfs*9) in the APC gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 809 amino acid(s) of the APC protein. |
| Ambry Genetics | RCV002352610 | SCV002660506 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2020-12-30 | criteria provided, single submitter | clinical testing | The c.6102delT pathogenic mutation, located in coding exon 15 of the APC gene, results from a deletion of one nucleotide at nucleotide position 6102, causing a translational frameshift with a predicted alternate stop codon (p.E2035Kfs*9). This alteration occurs at the 3' terminus of the APC gene, is not expected to trigger nonsense-mediated mRNA decay, but impacts ~28% of the protein. Premature stop codons are typically deleterious in nature and the impacted region is critical for protein function (Ambry internal data). Based on the majority of available evidence to date, this variant is likely to be pathogenic. |