ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.610G>A (p.Gly204Arg) (rs63750574)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000115537 SCV000149446 uncertain significance not provided 2018-11-21 criteria provided, single submitter clinical testing This variant is denoted MSH2 c.610G>A at the cDNA level, p.Gly204Arg (G204R) at the protein level, and results in the change of a Glycine to an Arginine (GGA>AGA). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. MSH2 Gly204Arg was not observed at a significant allele frequency in large population cohorts (Lek 2016). This variant is located within the connector domain (Lutzen 2008, Kansikas 2011). In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect. Based on currently available evidence, it is unclear whether MSH2 Gly204Arg is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000196378 SCV000254426 uncertain significance Hereditary nonpolyposis colon cancer 2018-10-25 criteria provided, single submitter clinical testing This sequence change replaces glycine with arginine at codon 204 of the MSH2 protein (p.Gly204Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with MSH2-related disease. 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"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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.
Ambry Genetics RCV000215932 SCV000274151 uncertain significance Hereditary cancer-predisposing syndrome 2017-06-19 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Counsyl RCV000411245 SCV000489688 uncertain significance Lynch syndrome I 2016-11-09 criteria provided, single submitter clinical testing
Color RCV000215932 SCV000905222 uncertain significance Hereditary cancer-predisposing syndrome 2018-04-25 criteria provided, single submitter clinical testing

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