ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.2927G>A (p.Arg976His) (rs63751113)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000218618 SCV000273877 likely pathogenic Hereditary cancer-predisposing syndrome 2018-02-06 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Deficient protein function in appropriate functional assay(s),In silico models in agreement (deleterious) and/or completely conserved position in appropriate species,Rarity in general population databases (dbsnp, esp, 1000 genomes),Other data supporting pathogenic classification
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000074787 SCV000107998 uncertain significance Lynch syndrome 2013-09-05 reviewed by expert panel research Insufficient evidence
Invitae RCV000629775 SCV000750731 uncertain significance Hereditary nonpolyposis colon cancer 2018-08-30 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 976 of the MSH6 protein (p.Arg976His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual affected with colorectal and kidney cell cancer (PMID: 11807791). ClinVar contains an entry for this variant (Variation ID: 89322). Experimental studies have shown that this missense change results in abnormal mismatch recognition, a reduced ability to bind ADP, reduced mismatch repair efficiency, and reduced ability to cross-link ATP to the hMSH2 subunit. (PMID: 18790734, 22102614). 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.
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000455514 SCV000539703 uncertain significance not specified 2016-03-28 criteria provided, single submitter clinical testing Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: ClinVar: VUS by expert panel; No new info since expert classification
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000455514 SCV000601547 uncertain significance not specified 2017-03-31 criteria provided, single submitter clinical testing

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