ClinVar Miner

Submissions for variant NM_004992.3(MECP2):c.343C>T (p.Arg115Cys) (rs267608388)

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 RCV000715718 SCV000846549 uncertain significance History of neurodevelopmental disorder 2016-05-06 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
GeneDx RCV000133074 SCV000191034 likely pathogenic not provided 2016-11-30 criteria provided, single submitter clinical testing A published R115C variant that is likely pathogenic has been identified in the MECP2 gene. The R115C missense variant was previously reported as a de novo variant in a female with classic Rett syndrome; however, this individual also had a de novo frameshift variant in the MECP2 gene (Bunyan et al., 2008). The R115C variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The R115C variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a conserved position predicted to be within the MBD domain. Missense variants in nearby residues (R111G, Y120D) have been reported in the Human Gene Mutation Database in association with Rett syndrome (Stenson et al., 2014). Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded.
RettBASE RCV000133074 SCV000188062 not provided not provided no assertion provided not provided

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.