ClinVar Miner

Submissions for variant NM_000038.6(APC):c.6976C>T (p.Arg2326Ter) (rs1060503355)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000460599 SCV000552730 pathogenic Familial adenomatous polyposis 1 2018-11-26 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the last exon of the APC mRNA at codon 2326 (p.Arg2326*). While this is not anticipated to result in nonsense mediated decay, it is expected to delete the last 518 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. ClinVar contains an entry for this variant (Variation ID: 411530). 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, c.7932_7935del (p.Tyr2645Lysfs*14), that lies downstream of this variant has been determined to be pathogenic (PMID: 9824584, 1316610, 27081525, 8381579, 22135120, Invitae). For these reasons, this variant has been classified as Pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000985316 SCV001133360 likely pathogenic not provided 2018-09-25 criteria provided, single submitter clinical testing The variant creates a premature nonsense codon, and is therefore predicted to significantly disrupt the protein structure. Not found in the total gnomAD dataset, and the data are high quality (0/276310 chr).

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.