ClinVar Miner

Submissions for variant NM_000179.3(MSH6):c.947G>A (p.Arg316Lys)

gnomAD frequency: 0.00001  dbSNP: rs562487553
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
Ambry Genetics RCV000562657 SCV000670115 uncertain significance Hereditary cancer-predisposing syndrome 2024-01-30 criteria provided, single submitter clinical testing The p.R316K variant (also known as c.947G>A), located in coding exon 4 of the MSH6 gene, results from a G to A substitution at nucleotide position 947. The arginine at codon 316 is replaced by lysine, an amino acid with highly similar properties. In a study of whole-exome sequencing in patients with features of Cowden syndrome (CS) or Bannayan-Riley-Ruvalcaba syndrome (BRRS) and negative PTEN testing, this alteration was identified in 0/87 patients with CS or BRRS and 1/3476 patients from The Cancer Genome Atlas (TCGA) (Yehia L et al. PLoS Genet, 2018 04;14:e1007352). This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Invitae RCV000630127 SCV000751083 benign Hereditary nonpolyposis colorectal neoplasms 2023-05-31 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000562657 SCV000908361 uncertain significance Hereditary cancer-predisposing syndrome 2019-07-26 criteria provided, single submitter clinical testing This missense variant replaces arginine with lysine at codon 316 of the MSH6 protein. Computational prediction tools and conservation analyses suggest that this variant may not impact the protein function. Computational splicing tools suggest that this variant may not impact RNA splicing. To our knowledge, functional assays have not been performed for this variant nor has this variant been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 2/251316 chromosomes in the general population by the Genome Aggregation Database (gnomAD). 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.
All of Us Research Program, National Institutes of Health RCV004001067 SCV004837447 uncertain significance Lynch syndrome 2023-11-30 criteria provided, single submitter clinical testing This missense variant replaces arginine with lysine at codon 316 of the MSH6 protein. Computational prediction tools and conservation analyses suggest that this variant may not impact the protein function. Computational splicing tools suggest that this variant may not impact RNA splicing. To our knowledge, functional assays have not been performed for this variant nor has this variant been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 2/251316 chromosomes in the general population by the Genome Aggregation Database (gnomAD). 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.