ClinVar Miner

Submissions for variant NM_000038.6(APC):c.5834del (p.Ala1945fs)

dbSNP: rs1766061264
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002562420 SCV001388938 pathogenic Familial adenomatous polyposis 1 2019-07-27 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. This sequence change results in a premature translational stop signal in the APC gene (p.Ala1945Glufs*25). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 899 amino acids of the APC protein. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with APC-related conditions. 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
Myriad Genetics, Inc. RCV002562420 SCV004045740 pathogenic Familial adenomatous polyposis 1 2023-05-15 criteria provided, single submitter clinical testing This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.
PreventionGenetics, part of Exact Sciences RCV003405401 SCV004115107 likely pathogenic APC-related disorder 2023-03-28 criteria provided, single submitter clinical testing The APC c.5834delC variant is predicted to result in a frameshift and premature protein termination (p.Ala1945Glufs*25). To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. Frameshift variants in APC are expected to be pathogenic, and others have been documented as causative both up and downstream. This variant is interpreted as likely pathogenic.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.