ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.1267C>G (p.Leu423Val) (rs587781657)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000129796 SCV000184605 uncertain significance Hereditary cancer-predisposing syndrome 2016-12-07 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence,In silico models in agreement (benign)
Invitae RCV000466742 SCV000551143 uncertain significance Hereditary nonpolyposis colon cancer 2018-03-05 criteria provided, single submitter clinical testing This sequence change replaces leucine with valine at codon 423 of the MSH6 protein (p.Leu423Val). The leucine residue is weakly conserved and there is a small physicochemical difference between leucine and valine. 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. ClinVar contains an entry for this variant (Variation ID: 141322). 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.
Integrated Genetics/Laboratory Corporation of America RCV000588684 SCV000695779 uncertain significance not provided 2016-04-18 criteria provided, single submitter clinical testing Variant summary: The MSH6 c.1267C>G variant affects a non-conserved nucleotide, resulting in amino acid change from Leu to Val. 3/3 in-silico tools predict benign outcome for this variant (SNPs&GO and Mutation Taster were not captured due to low reliability index/p-value). This variant was not found in 121330 control chromosomes. In addition, one clinical laboratory classified this variant as a VUS. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical laboratories; nor evaluated for functional impact by in vivo/vitro studies. Because of the absence of clinical information and the lack of functional studies, the variant was classified as a variant of uncertain significance (VUS) until additional information becomes available.

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.