ClinVar Miner

Submissions for variant NM_001110792.2(MECP2):c.554C>G (p.Pro185Arg) (rs267608492)

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
Genetic Services Laboratory,University of Chicago RCV000133149 SCV000247975 uncertain significance not specified 2016-03-04 criteria provided, single submitter clinical testing
Molecular Diagnostics Lab,Nemours Alfred I. duPont Hospital for Children RCV000192592 SCV000537173 uncertain significance Rett syndrome 2015-07-07 criteria provided, single submitter clinical testing
Invitae RCV000686598 SCV000814123 uncertain significance Severe neonatal-onset encephalopathy with microcephaly 2018-03-20 criteria provided, single submitter clinical testing This sequence change replaces proline with arginine at codon 173 of the MECP2 protein (p.Pro173Arg). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual with Rett syndrome as inherited from an unaffected mother with random X-chromosome inactivation, however, that individual also carried another variant that was de novo and in trans(on the opposite chromosome) with this variant (PMID: 23696494). ClinVar contains an entry for this variant (Variation ID: 143609). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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.
RettBASE RCV000133149 SCV000188141 uncertain significance not specified 2011-02-15 no assertion criteria provided curation

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.