ClinVar Miner

Submissions for variant NM_001048174.2(MUTYH):c.509G>A (p.Gly170Glu)

dbSNP: rs1645156886
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV001189225 SCV001356479 uncertain significance Hereditary cancer-predisposing syndrome 2019-12-10 criteria provided, single submitter clinical testing This missense variant replaces glycine with glutamic acid at codon 198 of the MUTYH protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed 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.
Ambry Genetics RCV001189225 SCV002653975 uncertain significance Hereditary cancer-predisposing syndrome 2021-02-24 criteria provided, single submitter clinical testing The p.G198E variant (also known as c.593G>A), located in coding exon 8 of the MUTYH gene, results from a G to A substitution at nucleotide position 593. The glycine at codon 198 is replaced by glutamic acid, an amino acid with similar properties. This amino acid position is not 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 RCV002560939 SCV003500721 uncertain significance Familial adenomatous polyposis 2 2023-08-18 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 198 of the MUTYH protein (p.Gly198Glu). This variant is not present in population databases (gnomAD no frequency). 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: 926550). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The glutamic acid 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.

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