ClinVar Miner

Submissions for variant NM_001048174.2(MUTYH):c.484G>T (p.Ala162Ser) (rs764458059)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000219640 SCV000277687 uncertain significance Hereditary cancer-predisposing syndrome 2018-12-26 criteria provided, single submitter clinical testing The p.A190S variant (also known as c.568G>T), located in coding exon 7 of the MUTYH gene, results from a G to T substitution at nucleotide position 568. The alanine at codon 190 is replaced by serine, an amino acid with similar properties. This amino acid position is highly 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 RCV000470639 SCV000545733 uncertain significance MYH-associated polyposis 2020-03-10 criteria provided, single submitter clinical testing This sequence change replaces alanine with serine at codon 190 of the MUTYH protein (p.Ala190Ser). The alanine residue is highly conserved and there is a moderate physicochemical difference between alanine and serine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with MUTYH-related disease. ClinVar contains an entry for this variant (Variation ID: 233334). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: Tolerated; PolyPhen-2: Probably Damaging; Align-GVGD: Class C0). 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.
Mendelics RCV000470639 SCV000837773 uncertain significance MYH-associated polyposis 2018-07-02 criteria provided, single submitter clinical testing
Color Health, Inc RCV000219640 SCV001358554 uncertain significance Hereditary cancer-predisposing syndrome 2020-12-21 criteria provided, single submitter clinical testing This missense variant replaces alanine with serine at codon 190 of the MUTYH protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001192932 SCV001361394 uncertain significance not specified 2019-10-21 criteria provided, single submitter clinical testing Variant summary: MUTYH c.568G>T (p.Ala190Ser) results in a conservative amino acid change located in the HhH-GPD domain of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251462 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.568G>T in individuals affected with MUTYH-associated Polyposis and no experimental evidence demonstrating its impact on protein function have been reported. Three ClinVar submissions (evaluation after 2014) cite the variant as uncertain significance. 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.