ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.3605T>C (p.Met1202Thr) (rs587779273)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000129370 SCV000184134 likely benign Hereditary cancer-predisposing syndrome 2016-10-03 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: In silico models in agreement (benign),Other strong data supporting benign classification
GeneDx RCV000212685 SCV000211323 uncertain significance not provided 2017-10-06 criteria provided, single submitter clinical testing This variant is denoted MSH6 c.3605T>C at the cDNA level, p.Met1202Thr (M1202T) 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 Met1202Thr was not observed at a significant allele frequency in large population cohorts (Lek 2016). Since Methionine and Threonine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. MSH6 Met1202Thr occurs at a position that is not conserved and is located in the ATPase domain (Warren 2007, Kansikas 2011). In silico analyses predict that this variant is unlikely to alter protein structure or function. Based on currently available evidence, it is unclear whether MSH6 Met1202Thr is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000524181 SCV000261076 uncertain significance Hereditary nonpolyposis colon cancer 2018-05-21 criteria provided, single submitter clinical testing This sequence change replaces methionine with threonine at codon 1202 of the MSH6 protein (p.Met1202Thr). The methionine residue is weakly conserved and there is a moderate physicochemical difference between methionine and threonine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual in the Leiden Open-source Variation Database (PMID: 21520333, 23443670). ClinVar contains an entry for this variant (Variation ID: 89424). An algorithm developed specifically for the MSH6 gene suggests that this missense change is likely to be tolerated (PMID: 22290698). 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.
Color RCV000129370 SCV000690379 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-04 criteria provided, single submitter clinical testing
Counsyl RCV000662842 SCV000785702 uncertain significance Hereditary nonpolyposis colorectal cancer type 5 2017-11-08 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000764434 SCV000895491 uncertain significance Endometrial carcinoma; Turcot syndrome; Hereditary nonpolyposis colorectal cancer type 5 2018-10-31 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.