ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.667C>G (p.Leu223Val) (rs1558461660)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Integrated Genetics/Laboratory Corporation of America RCV000781554 SCV000919689 uncertain significance not specified 2018-02-09 criteria provided, single submitter clinical testing Variant summary: MSH2 c.667C>G (p.Leu223Val) results in a conservative amino acid change located in the DNA mismatch repair protein MutS, connector domain of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant was absent in 245900 control chromosomes, thus the available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.667C>G in individuals affected with Lynch Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Co-occurrence with a pathogenic variant in an internal specimen has been reported (PMS2 c.2186_2187delTC, p.L729fsX6), providing supporting evidence for a benign role. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance.

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