ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.2266A>G (p.Thr756Ala) (rs750646335)

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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 RCV000565456 SCV000662225 uncertain significance Hereditary cancer-predisposing syndrome 2017-08-30 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000759112 SCV000888218 uncertain significance not provided 2018-05-17 criteria provided, single submitter clinical testing
Invitae RCV000793685 SCV000933050 uncertain significance Hereditary nonpolyposis colon cancer 2018-10-17 criteria provided, single submitter clinical testing This sequence change replaces threonine with alanine at codon 756 of the MSH2 protein (p.Thr756Ala). The threonine residue is highly conserved and there is a small physicochemical difference between threonine and alanine. This variant is present in population databases (rs750646335, ExAC 0.01%). This variant has not been reported in the literature in individuals with MSH2-related disease. ClinVar contains an entry for this variant (Variation ID: 479790). 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.

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