ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.2717T>C (p.Ile906Thr) (rs587780687)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000122988 SCV000166277 uncertain significance Hereditary nonpolyposis colon cancer 2018-12-03 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with threonine at codon 906 of the MSH2 protein (p.Ile906Thr). The isoleucine residue is weakly conserved and there is a moderate physicochemical difference between isoleucine and threonine. This variant is not present in population databases (rs587780687, ExAC no frequency) and has not been reported in the literature in individuals with an MSH2-related disease. ClinVar contains an entry for this variant (Variation ID: 135860). 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.
Counsyl RCV000412095 SCV000488246 uncertain significance Lynch syndrome I 2016-02-02 criteria provided, single submitter clinical testing
Ambry Genetics RCV000573859 SCV000662235 uncertain significance Hereditary cancer-predisposing syndrome 2017-05-05 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Color RCV000573859 SCV000690091 uncertain significance Hereditary cancer-predisposing syndrome 2018-07-14 criteria provided, single submitter clinical testing

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