ClinVar Miner

Submissions for variant NM_000038.6(APC):c.4645C>T (p.Gln1549Ter)

dbSNP: rs863225357
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002519589 SCV000829523 pathogenic Familial adenomatous polyposis 1 2021-12-24 criteria provided, single submitter clinical testing 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. 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. ClinVar contains an entry for this variant (Variation ID: 217986). This variant has not been reported in the literature in individuals affected with APC-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln1549*) in the APC gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 1295 amino acid(s) of the APC protein.
Myriad Genetics, Inc. RCV002519589 SCV004045682 pathogenic Familial adenomatous polyposis 1 2023-05-11 criteria provided, single submitter clinical testing This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation.
Mayo Clinic Laboratories, Mayo Clinic RCV000202166 SCV000257002 pathogenic not provided no assertion criteria provided research
Department of Pathology and Laboratory Medicine, Sinai Health System RCV000202166 SCV001550443 uncertain significance not provided no assertion criteria provided clinical testing
Martignetti Lab, Icahn School of Medicine at Mount Sinai RCV003327380 SCV004035001 association Atypical endometrial hyperplasia no assertion criteria provided research

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.