ClinVar Miner

Submissions for variant NM_000179.3(MSH6):c.3257C>A (p.Pro1086His)

dbSNP: rs780345806
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000482150 SCV000571204 uncertain significance not provided 2023-05-23 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 17531815, 21120944)
Invitae RCV000560746 SCV000624837 benign Hereditary nonpolyposis colorectal neoplasms 2023-12-08 criteria provided, single submitter clinical testing
Ambry Genetics RCV000570886 SCV000676109 uncertain significance Hereditary cancer-predisposing syndrome 2023-05-31 criteria provided, single submitter clinical testing The p.P1086H variant (also known as c.3257C>A), located in coding exon 5 of the MSH6 gene, results from a C to A substitution at nucleotide position 3257. The proline at codon 1086 is replaced by histidine, an amino acid with similar properties. 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.
Color Diagnostics, LLC DBA Color Health RCV000570886 SCV000685374 uncertain significance Hereditary cancer-predisposing syndrome 2023-05-04 criteria provided, single submitter clinical testing This missense variant replaces proline with histidine at codon 1086 of the MSH6 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, 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 4/251436 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.
All of Us Research Program, National Institutes of Health RCV004003362 SCV004835027 uncertain significance Lynch syndrome 2023-11-20 criteria provided, single submitter clinical testing This missense variant replaces proline with histidine at codon 1086 of the MSH6 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, 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 4/251436 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.