ClinVar Miner

Submissions for variant NM_000251.3(MSH2):c.2714C>G (p.Thr905Arg)

dbSNP: rs267608022
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000203618 SCV000107568 likely benign Lynch syndrome 1 2015-11-24 reviewed by expert panel research
Invitae RCV000076539 SCV000166276 benign Hereditary nonpolyposis colorectal neoplasms 2023-11-27 criteria provided, single submitter clinical testing
Ambry Genetics RCV000129528 SCV000184304 likely benign Hereditary cancer-predisposing syndrome 2020-01-06 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
GeneDx RCV000424772 SCV000518413 likely benign not provided 2018-09-11 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 32849802, 16995940, 26333163, 14526391, 20459533, 11162093, 22290698, 17101317, 8880570, 17594722, 12124176, 9774676, 24362816)
Mendelics RCV000203618 SCV001135763 benign Lynch syndrome 1 2019-05-28 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000129528 SCV001357010 likely benign Hereditary cancer-predisposing syndrome 2023-03-28 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV003997167 SCV004826653 uncertain significance Lynch syndrome 2023-06-28 criteria provided, single submitter clinical testing This missense variant replaces threonine with arginine at codon 905 of the MSH2 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). Functional studies have shown that this variant does not significantly impact MSH2 activity as determined by in vitro mismatch repair activity, ATPase activity and interaction with its binding partners (PMID: 9774676, 12124176). This variant has been reported in a family affected with hereditary non-polyposis colon cancer syndrome (PMID: 8880570). This variant has been identified in 3/282122 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

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