ClinVar Miner

Submissions for variant NM_000251.3(MSH2):c.1832T>A (p.Val611Glu)

dbSNP: rs1553368590
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
University of Washington Department of Laboratory Medicine, University of Washington RCV000664317 SCV000788253 likely pathogenic Lynch syndrome 2018-02-07 criteria provided, single submitter clinical testing The MSH2 p.V611E variant has not been previously reported, to our knowledge, and occurs at a position that is evolutionarily conserved. Testing performed on tumor tissue of a patient with germline MSH2 p.V611E supports that this variant is pathogenic. Specifically, in the patient's tumor the constitutional MSH2 variant was seen with a single somatic pathogenic mutation at heterozygous frequency in MSH2, without evidence loss of heterozygosity in MSH2.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV004702272 SCV005205174 uncertain significance not specified 2024-06-17 criteria provided, single submitter clinical testing Variant summary: MSH2 c.1832T>A (p.Val611Glu) results in a non-conservative amino acid change in DNA mismatch repair protein MutS, core domain (IPR007696) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251476 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1832T>A has been reported in the literature in one individual affected with Colon cancer and a somatic variant in MSH2 was also found in the tumor tissue (Pearlman_2017). However, the details of the somatic change were not provided. These report(s) do not provide unequivocal conclusions about association of the variant with Lynch Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 27978560). ClinVar contains an entry for this variant (Variation ID: 549765). Based on the evidence outlined above, the variant was classified as uncertain significance.

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