ClinVar Miner

Submissions for variant NM_001128425.1(MUTYH):c.961G>A (p.Gly321Arg) (rs765686051)

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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 RCV000219497 SCV000273585 likely benign Hereditary cancer-predisposing syndrome 2018-09-27 criteria provided, single submitter clinical testing In silico models in agreement (benign) ;Other strong data
Invitae RCV000540135 SCV000639367 uncertain significance MYH-associated polyposis 2020-09-23 criteria provided, single submitter clinical testing This sequence change replaces glycine with arginine at codon 321 of the MUTYH protein (p.Gly321Arg). The glycine residue is weakly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is present in population databases (rs765686051, ExAC 0.01%). This variant has not been reported in the literature in individuals with MUTYH-related disease. ClinVar contains an entry for this variant (Variation ID: 230146). 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 arginine 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.
Color Health, Inc RCV000219497 SCV001349593 uncertain significance Hereditary cancer-predisposing syndrome 2019-06-30 criteria provided, single submitter clinical testing
GeneDx RCV001551196 SCV001771655 uncertain significance not provided 2020-03-06 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

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