ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.260C>G (p.Ser87Cys) (rs587781447)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000129363 SCV000184127 uncertain significance Hereditary cancer-predisposing syndrome 2016-12-19 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
GeneDx RCV000212581 SCV000211179 uncertain significance not provided 2018-03-06 criteria provided, single submitter clinical testing This variant is denoted MSH2 c.260C>G at the cDNA level, p.Ser87Cys (S87C) at the protein level, and results in the change of a Serine to a Cysteine (TCT>TGT). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. MSH2 Ser87Cys was not observed at a significant allele frequency in large population cohorts (Lek 2016). MSH2 Ser87Cys 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 information, it is unclear whether MSH2 Ser87Cys is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000233259 SCV000284156 uncertain significance Hereditary nonpolyposis colon cancer 2018-10-11 criteria provided, single submitter clinical testing This sequence change replaces serine with cysteine at codon 87 of the MSH2 protein (p.Ser87Cys). The serine residue is highly conserved and there is a moderate physicochemical difference between serine and cysteine. This variant is present in population databases (rs587781447, ExAC 0.001%). This variant has been reported in an individual in the Leiden Open-source Variation Database (PMID: 21520333). ClinVar contains an entry for this variant (Variation ID: 141032). 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"). 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 RCV000129363 SCV000685065 uncertain significance Hereditary cancer-predisposing syndrome 2018-07-31 criteria provided, single submitter clinical testing
Counsyl RCV000662735 SCV000785507 uncertain significance Lynch syndrome I 2017-08-30 criteria provided, single submitter clinical testing

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