ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.891C>G (p.Ser297Arg) (rs551236465)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000236690 SCV000292934 uncertain significance not provided 2018-03-12 criteria provided, single submitter clinical testing This variant is denoted MSH2 c.891C>G at the cDNA level, p.Ser297Arg (S297R) at the protein level, and results in the change of a Serine to an Arginine (AGC>AGG). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. MSH2 Ser297Arg was not observed at a significant allele frequency in large population cohorts (Lek 2016). This variant is located in connector domain (L?tzen 2008). In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect. Based on currently available evidence, it is unclear whether MSH2 Ser297Arg is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000456430 SCV000548173 uncertain significance Hereditary nonpolyposis colon cancer 2018-10-13 criteria provided, single submitter clinical testing This sequence change replaces serine with arginine at codon 297 of the MSH2 protein (p.Ser297Arg). The serine residue is moderately conserved and there is a moderate physicochemical difference between serine 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. ClinVar contains an entry for this variant (Variation ID: 245802). 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: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C15"). 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 RCV000563882 SCV000664843 uncertain significance Hereditary cancer-predisposing syndrome 2018-05-02 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000236690 SCV000889444 uncertain significance not provided 2018-03-27 criteria provided, single submitter clinical testing
Color RCV000563882 SCV000908284 uncertain significance Hereditary cancer-predisposing syndrome 2018-06-09 criteria provided, single submitter clinical testing

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