ClinVar Miner

Submissions for variant NM_000179.3(MSH6):c.3818A>G (p.Asn1273Ser)

gnomAD frequency: 0.00001  dbSNP: rs201830316
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 RCV001021223 SCV001182809 uncertain significance Hereditary cancer-predisposing syndrome 2023-11-20 criteria provided, single submitter clinical testing The p.N1273S variant (also known as c.3818A>G), located in coding exon 9 of the MSH6 gene, results from an A to G substitution at nucleotide position 3818. The asparagine at codon 1273 is replaced by serine, an amino acid with highly similar properties. This amino acid position is highly 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.
Color Diagnostics, LLC DBA Color Health RCV001021223 SCV001344757 uncertain significance Hereditary cancer-predisposing syndrome 2021-05-10 criteria provided, single submitter clinical testing This missense variant replaces asparagine with serine at codon 1273 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 performed for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 1/245910 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.
Invitae RCV001861012 SCV002150538 likely benign Hereditary nonpolyposis colorectal neoplasms 2023-05-15 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV004004611 SCV004835146 uncertain significance Lynch syndrome 2023-05-31 criteria provided, single submitter clinical testing This missense variant replaces asparagine with serine at codon 1273 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 performed for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 1/245910 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.