ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.3977T>C (p.Met1326Thr) (rs757089977)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000480936 SCV000567411 uncertain significance not provided 2015-07-23 criteria provided, single submitter clinical testing This variant is denoted MSH6 c.3977T>C at the cDNA level, p.Met1326Thr (M1326T) at the protein level, and results in the change of a Methionine to a Threonine (ATG>ACG). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. MSH6 Met1326Thr was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Since Methionine and Threonine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. MSH6 Met1326Thr occurs at a position that is not conserved and is located in the MutS domain V (Terui 2013). A published in silico algorithm predicted this variant to be of uncertain significance, and in house in silico analyses are inconsistent regarding the effect this variant may have on protein structure and function (Terui 2013). Based on currently available information, it is unclear whether MSH6 Met1326Thr is pathogenic or benign. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV000574295 SCV000669986 uncertain significance Hereditary cancer-predisposing syndrome 2019-03-12 criteria provided, single submitter clinical testing Insufficient evidence

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.