ClinVar Miner

Submissions for variant NM_000038.6(APC):c.3179_3183del (p.Ile1060fs)

dbSNP: rs1554084794
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 1
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV004563423 SCV000768185 pathogenic Familial adenomatous polyposis 1 2018-12-03 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the APC gene (p.Ile1060Thrfs*3). While this is not anticipated to result in nonsense mediated decay, it is expected to delete the last 1782 amino acids (~63%) of the APC protein. This variant is not present in population databases (ExAC no frequency). This variant has been reported in families affected with familial adenomatous polyposis (PMID: 12010888). This variant is reported as a 5 bp deletion at codon 1059 in the literature. ClinVar contains an entry for this variant (Variation ID: 537504). 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. 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.

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.