ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.2768T>A (p.Val923Glu) (rs146421227)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000533753 SCV000625411 uncertain significance Hereditary nonpolyposis colon cancer 2018-06-11 criteria provided, single submitter clinical testing This sequence change replaces valine with glutamic acid at codon 923 of the MSH2 protein (p.Val923Glu). The valine residue is moderately conserved and there is a moderate physicochemical difference between valine and glutamic acid. This variant is present in population databases (rs146421227, ExAC 0.002%). This variant has been reported in the literature in individuals from several families affected with Lynch syndrome (PMID: 12112654, 21431882, 18566915, 17101317). ClinVar contains an entry for this variant (Variation ID: 91043). Experimental studies report contradictory results. This missense change was shown to cause a mild reduction in mismatch binding and release capacity of MSH2 (PMID: 18951462), but behaved as wild-type by mismatch repair activity in vitro (PMID: 17101317, 21431882) 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.
CSER_CC_NCGL; University of Washington Medical Center RCV000148640 SCV000190355 uncertain significance Colorectal cancer, non-polyposis 2014-06-01 no assertion criteria provided research

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