ClinVar Miner

Submissions for variant NM_000038.6(APC):c.6137del (p.Ala2046fs) (rs1561605385)

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
Invitae RCV000706346 SCV000835389 pathogenic Familial adenomatous polyposis 1 2018-02-05 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the APC gene (p.Ala2046Glufs*27). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 798 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 disease. This variant deletes a portion of the C-terminus of the APC protein, including the Basic Domain, the EB1 Binding Site, and the HDLG Binding Site, which mediate interactions with the cytoskeleton (PMID: 15311282, 17293347). A different truncating variant downstream of this variant, c.7932_7935del (p.Tyr2645Lysfs*14), that only removes the EB1 and HDLG binding sites has been reported in several individuals with familial adenomatous polyposis (FAP) and attenuated FAP (PMID: 1316610, 8381579, 9824584, 22135120). These observations suggest that the C-terminal portion of the protein is clinically important. 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.