ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.1361T>C (p.Ile454Thr) (rs1060502025)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000467391 SCV000548289 uncertain significance Hereditary nonpolyposis colon cancer 2018-10-02 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with threonine at codon 454 of the MSH2 protein (p.Ile454Thr). The isoleucine residue is moderately conserved and there is a moderate physicochemical difference between isoleucine and threonine. 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: 408536). 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 and their clinical significance is uncertain. 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 RCV000491177 SCV000580646 uncertain significance Hereditary cancer-predisposing syndrome 2017-08-12 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence,In silico models in agreement (deleterious) and/or completely conserved position in appropriate species

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