ClinVar Miner

Submissions for variant NM_001048174.2(MUTYH):c.1468A>C (p.Ser490Arg)

gnomAD frequency: 0.00001  dbSNP: rs1380281188
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
Ambry Genetics RCV000564579 SCV000670190 uncertain significance Hereditary cancer-predisposing syndrome 2017-09-20 criteria provided, single submitter clinical testing The p.S518R variant (also known as c.1552A>C), located in coding exon 16 of the MUTYH gene, results from an A to C substitution at nucleotide position 1552. The serine at codon 518 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV000801202 SCV000940968 uncertain significance Familial adenomatous polyposis 2 2022-05-12 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with arginine, which is basic and polar, at codon 518 of the MUTYH protein (p.Ser518Arg). This variant is present in population databases (no rsID available, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with MUTYH-related conditions. ClinVar contains an entry for this variant (Variation ID: 483938). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The arginine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV005000290 SCV005622962 uncertain significance not provided 2023-11-20 criteria provided, single submitter clinical testing The MUTYH c.1552A>C (p.Ser518Arg) variant has not been reported in individuals with MUTYH-related conditions in the published literature. The frequency of this variant in the general population, 0.000032 (1/31376 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant.

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.