ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.3191C>T (p.Ala1064Val) (rs369042519)

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 RCV000759861 SCV000149314 uncertain significance not provided 2015-11-24 criteria provided, single submitter clinical testing This variant is denoted MSH6 c.3191C>T at the cDNA level, p.Ala1064Val (A1064V) at the protein level, and results in the change of an Alanine to a Valine (GCT>GTT). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. MSH6 Ala1064Val was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Since Alanine and Valine share similar properties, this is considered a conservative amino acid substitution. MSH6 Ala1064Val occurs at a position that is not conserved across species and is located in MutS domain III (Terui 2013). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function (Terui 2013). Based on currently available evidence, it is unclear whether MSH6 Ala1064Val is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV000216009 SCV000277148 uncertain significance Hereditary cancer-predisposing syndrome 2015-07-14 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence,In silico models in agreement (deleterious) and/or completely conserved position in appropriate species
Color RCV000216009 SCV000690326 uncertain significance Hereditary cancer-predisposing syndrome 2018-09-19 criteria provided, single submitter clinical testing
Invitae RCV000691203 SCV000818951 uncertain significance Hereditary nonpolyposis colon cancer 2018-05-09 criteria provided, single submitter clinical testing This sequence change replaces alanine with valine at codon 1064 of the MSH6 protein (p.Ala1064Val). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and valine. This variant is present in population databases (rs369042519, ExAC 0.02%). This variant has not been reported in the literature in individuals with MSH6-related disease. ClinVar contains an entry for this variant (Variation ID: 127581). An algorithm developed specifically for the MSH6 gene suggests that this missense change is likely to be deleterious (PMID: 23621914). However, this prediction has not been confirmed by published functional studies and its clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000759861 SCV000889486 uncertain significance not provided 2017-09-26 criteria provided, single submitter clinical testing

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.