ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.571C>T (p.Leu191Phe) (rs1553350898)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000504099 SCV000595831 uncertain significance not specified 2016-10-27 criteria provided, single submitter clinical testing
Color RCV000776712 SCV000912341 uncertain significance Hereditary cancer-predisposing syndrome 2019-06-12 criteria provided, single submitter clinical testing
Invitae RCV001244733 SCV001417975 uncertain significance Hereditary nonpolyposis colon cancer 2019-11-01 criteria provided, single submitter clinical testing This sequence change replaces leucine with phenylalanine at codon 191 of the MSH2 protein (p.Leu191Phe). The leucine residue is moderately conserved and there is a small physicochemical difference between leucine and phenylalanine. 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 conditions. ClinVar contains an entry for this variant (Variation ID: 435892). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant disrupts the p.Leu191 amino acid residue in MSH2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 22949379, 20587412, 19267393). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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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