ClinVar Miner

Submissions for variant NM_001048174.2(MUTYH):c.167A>G (p.Tyr56Cys) (rs200747973)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 7
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000131672 SCV000186704 uncertain significance Hereditary cancer-predisposing syndrome 2020-03-03 criteria provided, single submitter clinical testing The p.Y84C variant (also known as c.251A>G), located in coding exon 3 of the MUTYH gene, results from an A to G substitution at nucleotide position 251. The tyrosine at codon 84 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Invitae RCV000471221 SCV000545736 uncertain significance MYH-associated polyposis 2020-10-03 criteria provided, single submitter clinical testing This sequence change replaces tyrosine with cysteine at codon 84 of the MUTYH protein (p.Tyr84Cys). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and cysteine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with a MUTYH-related disease. ClinVar contains an entry for this variant (Variation ID: 41758). 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 disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, this variant has uncertain impact on MUTYH function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Color Health, Inc RCV000131672 SCV000685607 uncertain significance Hereditary cancer-predisposing syndrome 2020-02-21 criteria provided, single submitter clinical testing
Counsyl RCV000471221 SCV000794694 uncertain significance MYH-associated polyposis 2017-10-13 criteria provided, single submitter clinical testing
Mendelics RCV000471221 SCV000837784 uncertain significance MYH-associated polyposis 2018-07-02 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000471221 SCV001257712 uncertain significance MYH-associated polyposis 2018-01-12 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000034675 SCV000043378 variant of unknown significance not provided 2012-07-13 no assertion criteria provided research Converted during submission to 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.