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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