ClinVar Miner

Submissions for variant NM_000179.3(MSH6):c.-18G>T

gnomAD frequency: 0.00027  dbSNP: rs199913053
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 9
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000132459 SCV000187553 likely benign Hereditary cancer-predisposing syndrome 2019-01-18 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
GeneDx RCV000212623 SCV000211372 benign not specified 2014-06-17 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Color Diagnostics, LLC DBA Color Health RCV000132459 SCV000910595 likely benign Hereditary cancer-predisposing syndrome 2022-01-02 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000212623 SCV000917759 benign not specified 2018-04-13 criteria provided, single submitter clinical testing Variant summary: MSH6 c.-18G>T is located in the untranslated mRNA region upstream of the initiation codon. The variant was observed with an allele frequency of 0.0003 in 270744 control chromosomes (gnomAD). The observed variant frequency is approximately 2-folds higher than the estimated maximal expected allele frequency for a pathogenic variant in MSH6 causing Lynch Syndrome phenotype (0.00014), strongly suggesting that the variant is benign. The variant, c.-18G>T, has been reported in the literature in an individual affected with Lynch Syndrome (Lamberti_2006). These report(s) do not provide unequivocal conclusions about association of the variant with Lynch Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. A ClinVar submission from a clinical diagnostic laboratory (evaluation after 2014) cites the variant as "likely benign." Based on the evidence outlined above, the variant was classified as benign.
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden RCV001698958 SCV002010122 uncertain significance not provided 2021-11-03 criteria provided, single submitter clinical testing
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital RCV000212623 SCV002760652 likely benign not specified 2023-08-15 criteria provided, single submitter clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario RCV003149715 SCV003837634 likely benign Breast and/or ovarian cancer 2023-05-05 criteria provided, single submitter clinical testing
Clinical Genetics, Academic Medical Center RCV001698958 SCV001925567 likely benign not provided no assertion criteria provided clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ RCV001698958 SCV001951100 likely benign not provided no assertion criteria provided 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.