ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.364G>A (p.Glu122Lys) (rs143036974)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 7
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000212630 SCV000211353 likely benign not provided 2019-01-07 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 23621914)
Ambry Genetics RCV000160719 SCV000215491 uncertain significance Inborn genetic diseases 2016-07-28 criteria provided, single submitter clinical testing
Invitae RCV000197561 SCV000254318 likely benign Hereditary nonpolyposis colorectal neoplasms 2020-11-16 criteria provided, single submitter clinical testing
Counsyl RCV000411966 SCV000487888 uncertain significance Hereditary nonpolyposis colorectal cancer type 5 2015-11-25 criteria provided, single submitter clinical testing
Color Health, Inc RCV000776349 SCV000911715 likely benign Hereditary cancer-predisposing syndrome 2015-12-14 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000780470 SCV000917743 likely benign not specified 2018-02-16 criteria provided, single submitter clinical testing Variant summary: MSH6 c.364G>A (p.Glu122Lys) results in a conservative amino acid change located in the PWWP domain of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The observed variant frequency within Latino control individuals in the gnomAD database is approximately 4 fold above the estimated maximal expected allele frequency for a pathogenic variant in MSH6 causing Lynch Syndrome phenotype (0.00014), strongly suggesting the variant is a benign polymorphism found primarily in populations of Latino origin. The c.364G>A variant has been reported in two publications without strong evidence for pathogenicity; thus, these reports do not provide unequivocal conclusions about an association of the variant with Lynch Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All of these laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as likely benign.
Ambry Genetics RCV000776349 SCV001182330 uncertain significance Hereditary cancer-predisposing syndrome 2020-09-25 criteria provided, single submitter clinical testing The p.E122K variant (also known as c.364G>A), located in coding exon 2 of the MSH6 gene, results from a G to A substitution at nucleotide position 364. The glutamic acid at codon 122 is replaced by lysine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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.