Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV004564419 | SCV000832152 | pathogenic | Familial adenomatous polyposis 1 | 2021-10-07 | criteria provided, single submitter | clinical testing | 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. 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. ClinVar contains an entry for this variant (Variation ID: 579870). This variant has not been reported in the literature in individuals affected 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.Gly1836Glufs*27) in the APC gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 1008 amino acid(s) of the APC protein. |
| Color Diagnostics, |
RCV001805818 | SCV002051968 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2021-04-02 | criteria provided, single submitter | clinical testing | This variant deletes 1 nucleotide in exon 16 of the APC gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. To our knowledge, this variant has not been reported in individuals affected with hereditary cancer in the literature. 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 Likely Pathogenic. |
| Myriad Genetics, |
RCV004564419 | SCV004045527 | pathogenic | Familial adenomatous polyposis 1 | 2023-05-12 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation. |