ClinVar Miner

Submissions for variant NM_001128425.1(MUTYH):c.564G>C (p.Glu188Asp) (rs1335408660)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000567650 SCV000662632 uncertain significance Hereditary cancer-predisposing syndrome 2020-09-02 criteria provided, single submitter clinical testing The p.E188D variant (also known as c.564G>C), located in coding exon 7 of the MUTYH gene, results from a G to C substitution at nucleotide position 564. The glutamic acid at codon 188 is replaced by aspartic acid, an amino acid with highly similar properties. This amino acid position is 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000589262 SCV000697703 uncertain significance not specified 2019-03-12 criteria provided, single submitter clinical testing Variant summary: MUTYH c.564G>C (p.Glu188Asp) results in a conservative amino acid change located in the HhH-GPD domain (IPR003265) of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 4.1e-06 in 246272 control chromosomes (gnomAD). 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.564G>C in individuals affected with MUTYH-associated Polyposis and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Invitae RCV000801439 SCV000941215 uncertain significance MYH-associated polyposis 2020-04-26 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with aspartic acid at codon 188 of the MUTYH protein (p.Glu188Asp). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and aspartic acid. 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 conditions. ClinVar contains an entry for this variant (Variation ID: 480000). 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.
Color Health, Inc RCV000567650 SCV001353492 uncertain significance Hereditary cancer-predisposing syndrome 2019-11-12 criteria provided, single submitter clinical testing

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