ClinVar Miner

Submissions for variant NM_001110792.2(MECP2):c.1466G>C (p.Ser489Thr) (rs267608328)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001206116 SCV001377408 uncertain significance Severe neonatal-onset encephalopathy with microcephaly 2019-09-10 criteria provided, single submitter clinical testing This sequence change replaces serine with threonine at codon 477 of the MECP2 protein (p.Ser477Thr). The serine residue is highly conserved and there is a small physicochemical difference between serine and threonine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals with Rett syndrome or intellectual disability (PMID: 12655490, 17383248). However, in one of these individuals a pathogenic allele was also identified in MECP2, which suggests that the p.Ser477Thr variant was not the primary cause of disease. ClinVar contains an entry for this variant (Variation ID: 143475). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Not available"; 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.
RettBASE RCV000133005 SCV000187992 benign not specified 2007-11-01 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.