ClinVar Miner

Submissions for variant NM_000251.3(MSH2):c.727C>T (p.Arg243Trp)

gnomAD frequency: 0.00001  dbSNP: rs138857091
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 9
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000466771 SCV000548137 benign Hereditary nonpolyposis colorectal neoplasms 2024-01-31 criteria provided, single submitter clinical testing
Ambry Genetics RCV000570120 SCV000662220 uncertain significance Hereditary cancer-predisposing syndrome 2022-06-13 criteria provided, single submitter clinical testing The p.R243W variant (also known as c.727C>T), located in coding exon 4 of the MSH2 gene, results from a C to T substitution at nucleotide position 727. The arginine at codon 243 is replaced by tryptophan, an amino acid with dissimilar properties. This alteration was seen in 0/732 breast cancer patients, 1/189 colorectal cancer patients and 0/490 cancer-free elderly controls in a Turkish population (Akcay IM et al. Int J Cancer, 2021 01;148:285-295). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Color Diagnostics, LLC DBA Color Health RCV000570120 SCV000685125 uncertain significance Hereditary cancer-predisposing syndrome 2023-09-01 criteria provided, single submitter clinical testing This variant is located in the MSH2 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in individuals affected with colorectal cancer (PMID: 32658311). This variant has been identified in 4/282708 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.
GeneDx RCV001591088 SCV001814739 uncertain significance not provided 2023-04-24 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 individuals with a personal history of advanced cancers and colon cancer (Madelker et al., 2017; Akcay et al., 2020); This variant is associated with the following publications: (PMID: 18822302, 21120944, 28873162, 32658311)
Genetic Services Laboratory, University of Chicago RCV001821275 SCV002070916 uncertain significance not specified 2019-07-12 criteria provided, single submitter clinical testing
AiLife Diagnostics, AiLife Diagnostics RCV001591088 SCV002502496 uncertain significance not provided 2021-10-11 criteria provided, single submitter clinical testing
Sema4, Sema4 RCV000570120 SCV002534558 uncertain significance Hereditary cancer-predisposing syndrome 2021-10-21 criteria provided, single submitter curation
Baylor Genetics RCV003463904 SCV004194548 uncertain significance Lynch syndrome 1 2024-03-13 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV004000774 SCV004829027 uncertain significance Lynch syndrome 2023-09-17 criteria provided, single submitter clinical testing This variant is located in the MSH2 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in individuals affected with colorectal cancer (PMID: 32658311). This variant has been identified in 4/282708 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.