ClinVar Miner

Submissions for variant NM_000179.3(MSH6):c.746G>C (p.Arg249Thr)

dbSNP: rs752135996
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000552704 SCV000625000 likely benign Hereditary nonpolyposis colorectal neoplasms 2023-11-10 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000777228 SCV000912919 uncertain significance Hereditary cancer-predisposing syndrome 2023-09-06 criteria provided, single submitter clinical testing This missense variant replaces arginine with threonine at codon 249 of the MSH6 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). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with MSH6-related disorders in the literature. This variant has been identified in 1/251150 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.
Ambry Genetics RCV000777228 SCV002674153 uncertain significance Hereditary cancer-predisposing syndrome 2023-02-17 criteria provided, single submitter clinical testing The p.R249T variant (also known as c.746G>C), located in coding exon 4 of the MSH6 gene, results from a G to C substitution at nucleotide position 746. The arginine at codon 249 is replaced by threonine, an amino acid with similar properties. 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.
All of Us Research Program, National Institutes of Health RCV004003703 SCV004836974 uncertain significance Lynch syndrome 2023-10-02 criteria provided, single submitter clinical testing This missense variant replaces arginine with threonine at codon 249 of the MSH6 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). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 1/251150 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.