ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.1053G>C (p.Met351Ile) (rs373122667)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000131405 SCV000186381 uncertain significance Hereditary cancer-predisposing syndrome 2013-08-08 criteria provided, single submitter clinical testing
Invitae RCV000552818 SCV000625222 uncertain significance Hereditary nonpolyposis colon cancer 2017-02-15 criteria provided, single submitter clinical testing This sequence change replaces methionine with isoleucine at codon 351 of the MSH2 protein (p.Met351Ile). The methionine residue is moderately conserved and there is a small physicochemical difference between methionine and isoleucine. This variant is present in population databases (rs373122667, ExAC 0.001%) but has not been reported in the literature in individuals with a MSH2-related disease. ClinVar contains an entry for this variant (Variation ID: 142335). 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 tolerated, but these predictions have not been confirmed by published functional studies. In summary, this variant is a rare missense change that is not predicted to affect 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.
Color RCV000131405 SCV000684900 uncertain significance Hereditary cancer-predisposing syndrome 2018-10-21 criteria provided, single submitter clinical testing

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