ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.163C>G (p.Arg55Gly) (rs587782354)

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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 RCV000131300 SCV000186272 uncertain significance Hereditary cancer-predisposing syndrome 2017-11-14 criteria provided, single submitter clinical testing Insufficient or conflicting evidence
GeneDx RCV000212579 SCV000211240 uncertain significance not provided 2018-06-15 criteria provided, single submitter clinical testing This variant is denoted MSH2 c.163C>G at the cDNA level, p.Arg55Gly (R55G) at the protein level, and results in the change of an Arginine to a Glycine (CGG>GGG). This variant resulted in reduced or absent MSH2 mRNA and protein expression in transfected cell lines (Arora 2017). MSH2 Arg55Gly was not observed at a significant frequency in large population cohorts (Lek 2016). This variant is located in the mismatch binding 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 Arg55Gly is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000545235 SCV000625289 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2019-12-05 criteria provided, single submitter clinical testing This sequence change replaces arginine with glycine at codon 55 of the MSH2 protein (p.Arg55Gly). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and glycine. This variant is present in population databases (rs587782354, ExAC 0.008%). This variant has not been reported in the literature in individuals with MSH2-related conditions. ClinVar contains an entry for this variant (Variation ID: 142277). This variant has been reported to affect MSH2 protein function (PMID: 28494185). 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 RCV000131300 SCV000684957 uncertain significance Hereditary cancer-predisposing syndrome 2019-06-13 criteria provided, single submitter clinical testing

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