Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000411669 | SCV000488383 | pathogenic | Familial adenomatous polyposis 1 | 2016-03-17 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000657193 | SCV000778916 | pathogenic | not provided | 2021-08-19 | criteria provided, single submitter | clinical testing | Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (Lek 2016); Observed in individuals with Familial Adenomatous Polyposis in published literature (Lagarde 2010); This variant is associated with the following publications: (PMID: 20685668, 26309368, 10923044, 23085758, 8187091, 23766371) |
Invitae | RCV003535696 | SCV002227840 | pathogenic | Familial adenomatous polyposis 1 | 2021-08-04 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 371830). 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. For these reasons, this variant has been classified as Pathogenic. This premature translational stop signal has been observed in individual(s) with clinical features of familial adenomatous polyposis (PMID: 20685668). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Pro1319Leufs*2) in the APC gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 1525 amino acid(s) of the APC protein. |
Myriad Genetics, |
RCV000411669 | SCV004018219 | pathogenic | Familial adenomatous polyposis 1 | 2023-02-14 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation. |
Genome Sciences Centre, |
RCV001789774 | SCV000693733 | pathogenic | Colorectal cancer | 2016-04-12 | no assertion criteria provided | research |