ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.2992T>A (p.Ser998Thr) (rs730881800)

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
GeneDx RCV000160685 SCV000211306 uncertain significance not provided 2014-08-15 criteria provided, single submitter clinical testing This variant is denoted MSH6 c.2992T>A at the cDNA level, p.Ser998Thr (S998T) at the protein level, and results in the change of a Serine to a Threonine (TCT>ACT). This variant has been observed in an individual with rectal cancer at the age of 45 (Limburg 2011). MSH6 Ser998Thr 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 Serine and Threonine share similar properties, this is considered a conservative amino acid substitution. MSH6 Ser998Thr occurs at a position that is well conserved across species and is located in domain IV of the MutS domain (Terui 2013). In silico analyses predict that this variant is probably damaging to protein structure and function. Based on currently available information, it is unclear whether MSH6 Ser998Thr is pathogenic or benign. We consider it to be a variant of uncertain significance.
Invitae RCV000168112 SCV000218768 uncertain significance Hereditary nonpolyposis colon cancer 2019-12-19 criteria provided, single submitter clinical testing This sequence change replaces serine with threonine at codon 998 of the MSH6 protein (p.Ser998Thr). The serine residue is highly conserved and there is a small physicochemical difference between serine and threonine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual affected with colorectal cancer (PMID: 21056691). ClinVar contains an entry for this variant (Variation ID: 182639). 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.
Color RCV000579908 SCV000685345 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-30 criteria provided, single submitter clinical testing
Counsyl RCV000662434 SCV000784890 uncertain significance Hereditary nonpolyposis colorectal cancer type 5 2017-01-27 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000160685 SCV001152296 uncertain significance not provided 2019-01-01 criteria provided, single submitter clinical testing
Ambry Genetics RCV000579908 SCV001178986 uncertain significance Hereditary cancer-predisposing syndrome 2018-10-18 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.