ClinVar Miner

Submissions for variant NM_000038.6(APC):c.1566G>A (p.Met522Ile)

dbSNP: rs1763872461
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV003773367 SCV002290957 uncertain significance Familial adenomatous polyposis 1 2020-12-03 criteria provided, single submitter clinical testing This sequence change replaces methionine with isoleucine at codon 522 of the APC protein (p.Met522Ile). The methionine residue is highly conserved and there is a small physicochemical difference between methionine and isoleucine. 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 conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Sema4, Sema4 RCV002256886 SCV002527445 uncertain significance Hereditary cancer-predisposing syndrome 2021-06-23 criteria provided, single submitter curation
Ambry Genetics RCV002256886 SCV005038083 uncertain significance Hereditary cancer-predisposing syndrome 2024-04-24 criteria provided, single submitter clinical testing The p.M522I variant (also known as c.1566G>A), located in coding exon 12 of the APC gene, results from a G to A substitution at nucleotide position 1566. The methionine at codon 522 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, in silico predictors for this gene do not accurately predict pathogenicity. Missense alterations in APC are not a common cause of disease (Spier I et al. Genet Med. 2024 Feb;26(2):100992). Based on the available evidence, the clinical significance of this variant remains unclear.

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.