ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.934C>G (p.Leu312Val) (rs756398636)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000205023 SCV000259599 uncertain significance Hereditary nonpolyposis colon cancer 2018-09-21 criteria provided, single submitter clinical testing This sequence change replaces leucine with valine at codon 312 of the MSH2 protein (p.Leu312Val). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and valine. This variant is present in population databases (rs756398636, ExAC 0.003%). This variant has not been reported in the literature in individuals with MSH2-related disease. ClinVar contains an entry for this variant (Variation ID: 219619). 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 RCV000565881 SCV000662208 uncertain significance Hereditary cancer-predisposing syndrome 2016-08-02 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Color RCV000565881 SCV000690141 uncertain significance Hereditary cancer-predisposing syndrome 2018-10-21 criteria provided, single submitter clinical testing
Counsyl RCV000662459 SCV000784940 uncertain significance Lynch syndrome I 2017-02-09 criteria provided, single submitter clinical testing

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