ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.183G>T (p.Gln61His) (rs751082926)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000216596 SCV000277898 uncertain significance Hereditary cancer-predisposing syndrome 2018-04-24 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Invitae RCV000537297 SCV000625322 uncertain significance Hereditary nonpolyposis colon cancer 2018-10-16 criteria provided, single submitter clinical testing This sequence change replaces glutamine with histidine at codon 61 of the MSH2 protein (p.Gln61His). The glutamine residue is weakly conserved and there is a small physicochemical difference between glutamine and histidine. This variant is present in population databases (rs751082926, ExAC 0.3%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has been reported in a family affected with Lynch syndrome (PMID: 27601186). ClinVar contains an entry for this variant (Variation ID: 233513). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, this variant has uncertain impact on MSH2 function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Color RCV000216596 SCV000684984 uncertain significance Hereditary cancer-predisposing syndrome 2018-06-15 criteria provided, single submitter clinical testing
GeneKor MSA RCV000216596 SCV000822051 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-01 criteria provided, single submitter clinical testing

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