Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory of Molecular and Cellular Biology, |
RCV001845050 | SCV002104263 | pathogenic | Familial adenomatous polyposis 1 | criteria provided, single submitter | clinical testing | ||
Invitae | RCV003337300 | SCV003439190 | pathogenic | Familial adenomatous polyposis 1 | 2022-02-06 | criteria provided, single submitter | clinical testing | This premature translational stop signal has been observed in individual(s) with familial adenomatous polyposis (FAP) (PMID: 19444466, 20685668). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Lys1462Glufs*6) in the APC gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 1382 amino acid(s) of the APC protein. ClinVar contains an entry for this variant (Variation ID: 433661). 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. |
Myriad Genetics, |
RCV003337300 | SCV004044042 | pathogenic | Familial adenomatous polyposis 1 | 2023-05-10 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation. |
Department of Pathology and Laboratory Medicine, |
RCV000503564 | SCV000591170 | uncertain significance | not provided | no assertion criteria provided | clinical testing |