ClinVar Miner

Submissions for variant NM_000038.6(APC):c.2485del (p.Thr829fs)

dbSNP: rs1561577476
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV004564317 SCV000820878 pathogenic Familial adenomatous polyposis 1 2019-11-10 criteria provided, single submitter clinical testing This variant is not present in population databases (ExAC no frequency). This sequence change results in a premature translational stop signal in the APC gene (p.Thr829Glnfs*13). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 2015 amino acids (~70%) of the APC protein. For these reasons, this variant has been classified as Pathogenic. Several different truncations downstream of this variant (p.Ser932*, p.Ala1050Glufs*6, and p.Gln1062*) have been determined to be pathogenic (PMID: 20685668, 23460355, 15771908). This suggests that deletion of this region of the APC protein is causative of disease. This variant has not been reported in the literature in individuals with APC-related disease. ClinVar contains an entry for this variant (Variation ID: 571789).
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000755824 SCV000883411 pathogenic not provided 2018-04-26 criteria provided, single submitter clinical testing The APC c.2485delA; p.Thr829fs variant, to our knowledge, is not reported in the medical literature or gene specific databases. This variant is also absent from general population databases (1000 Genomes Project, Exome Variant Server, and Genome Aggregation Database), indicating it is not a common polymorphism. This variant causes a frameshift by deleting a single nucleotide, so it is predicted to result in a truncated protein. The vast majority of pathogenic APC variants are truncating nonsense or frameshift variants (see InSiGHt, Kerr 2013). Based on available information, the c.2485delA variant is considered to be pathogenic. REFERENCES Link to InSiGHt: https://www.insight-group.org/syndromes/adenomatous-polyposis/. Kerr SE et al. APC germline mutations in individuals being evaluated for familial adenomatous polyposis: a review of the Mayo Clinic experience with 1591 consecutive tests. J Mol Diagn. 2013 Jan;15(1):31-43.

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