ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.1114T>G (p.Leu372Val) (rs770201760)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color RCV000579817 SCV000684904 uncertain significance Hereditary cancer-predisposing syndrome 2019-05-10 criteria provided, single submitter clinical testing
Invitae RCV000821374 SCV000962129 uncertain significance Hereditary nonpolyposis colon cancer 2019-10-16 criteria provided, single submitter clinical testing This sequence change replaces leucine with valine at codon 372 of the MSH2 protein (p.Leu372Val). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and valine. This variant is present in population databases (rs770201760, ExAC 0.002%). This variant has not been reported in the literature in individuals with MSH2-related conditions. ClinVar contains an entry for this variant (Variation ID: 489910). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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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