ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.656G>C (p.Arg219Thr) (rs878853821)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000233640 SCV000284176 uncertain significance Hereditary nonpolyposis colon cancer 2017-05-19 criteria provided, single submitter clinical testing This sequence change replaces arginine with threonine at codon 219 of the MSH2 protein (p.Arg219Thr). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and threonine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a MSH2-related disease. ClinVar contains an entry for this variant (Variation ID: 237401). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies. In summary, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.

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