ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.37A>G (p.Lys13Glu) (rs942019524)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000458039 SCV000551119 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2018-03-20 criteria provided, single submitter clinical testing This sequence change replaces lysine with glutamic acid at codon 13 of the MSH6 protein (p.Lys13Glu). The lysine residue is highly conserved and there is a small physicochemical difference between lysine and glutamic acid. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with MSH6-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). 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.
GeneDx RCV000479706 SCV000569961 uncertain significance not provided 2016-04-13 criteria provided, single submitter clinical testing This variant is denoted MSH6 c.37A>G at the cDNA level, p.Lys13Glu (K13E) at the protein level, and results in the change of a Lysine to a Glutamic Acid (AAG>GAG). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. MSH6 Lys13Glu 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 Lysine and Glutamic Acid differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. MSH6 Lys13Glu occurs at a position that is conserved in mammals and is not located in a known functional domain (Kariola 2002, Terui 2013). In silico analyses predict that this variant is probably damaging to protein structure and function. Based on currently available evidence, it is unclear whether MSH6 Lys13Glu is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV000575714 SCV000662370 uncertain significance Hereditary cancer-predisposing syndrome 2018-03-21 criteria provided, single submitter clinical testing Insufficient or conflicting evidence
Color RCV000575714 SCV000690400 uncertain significance Hereditary cancer-predisposing syndrome 2019-03-18 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.