ClinVar Miner

Submissions for variant NM_001128425.1(MUTYH):c.125A>G (p.Asn42Ser) (rs563275223)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000131452 SCV000186436 likely benign Hereditary cancer-predisposing syndrome 2018-09-05 criteria provided, single submitter clinical testing In silico models in agreement (benign) ;Other strong data
Color Health, Inc RCV000131452 SCV000905868 likely benign Hereditary cancer-predisposing syndrome 2017-02-28 criteria provided, single submitter clinical testing
Invitae RCV000824066 SCV000964947 uncertain significance MYH-associated polyposis 2020-08-15 criteria provided, single submitter clinical testing This sequence change replaces asparagine with serine at codon 42 of the MUTYH protein (p.Asn42Ser). The asparagine residue is weakly conserved and there is a small physicochemical difference between asparagine and serine. This variant is present in population databases (rs563275223, ExAC 0.03%). This variant has been observed in an individual affected with familial adenomatous polyposis (PMID: 23460355). ClinVar contains an entry for this variant (Variation ID: 142369). 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 serine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001194163 SCV001363475 uncertain significance not specified 2019-06-17 criteria provided, single submitter clinical testing Variant summary: MUTYH c.125A>G (p.Asn42Ser) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 1.6e-05 in 251488 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.125A>G has been reported in the literature in one individual affected with MUTYH-associated Polyposis (Cruz-Correa_2013). This report does not provide unequivocal conclusions about association of the variant with MUTYH-associated Polyposis. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Both laboratories classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as uncertain significance.

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.