ClinVar Miner

Submissions for variant NM_000251.3(MSH2):c.891C>G (p.Ser297Arg)

gnomAD frequency: 0.00004  dbSNP: rs551236465
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 7
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000236690 SCV000292934 uncertain significance not provided 2023-08-18 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Observed in an individual with endometrial cancer in published literature (Scott et al., 2022); Published functional studies suggest this variant has no damaging effect based on results of an assay measuring resistance to 6-TG (Jia et al., 2020); This variant is associated with the following publications: (PMID: 18822302, 21120944, 33357406, 36550560)
Labcorp Genetics (formerly Invitae), Labcorp RCV000456430 SCV000548173 benign Hereditary nonpolyposis colorectal neoplasms 2024-12-12 criteria provided, single submitter clinical testing
Ambry Genetics RCV000563882 SCV000664843 uncertain significance Hereditary cancer-predisposing syndrome 2023-06-14 criteria provided, single submitter clinical testing The p.S297R variant (also known as c.891C>G), located in coding exon 5 of the MSH2 gene, results from a C to G substitution at nucleotide position 891. The serine at codon 297 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000236690 SCV000889444 uncertain significance not provided 2018-03-27 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000563882 SCV000908284 uncertain significance Hereditary cancer-predisposing syndrome 2019-06-12 criteria provided, single submitter clinical testing
Baylor Genetics RCV003463695 SCV004196243 uncertain significance Lynch syndrome 1 2023-09-20 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV004806269 SCV005429069 uncertain significance Lynch syndrome 2024-07-29 criteria provided, single submitter clinical testing This missense variant replaces serine with arginine at codon 297 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). This variant does not impact MSH2 function in a 6-thioguanine sensitivity assay in haploid human cells (internally defined LOF score threshold <= -1.32, PMID: 33357406). This variant has been reported in an individual affected with uterine and/or endometrial cancer (PMID: 36550560). This variant has been identified in 3/279824 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.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.