ClinVar Miner

Submissions for variant NM_001110792.2(MECP2):c.766C>T (p.Gln256Ter)

dbSNP: rs61749747
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000178228 SCV000230253 pathogenic not provided 2013-11-12 criteria provided, single submitter clinical testing
Genetic Services Laboratory, University of Chicago RCV000168689 SCV000247990 pathogenic Rett syndrome 2013-11-15 criteria provided, single submitter clinical testing
3billion RCV000168689 SCV002012225 pathogenic Rett syndrome 2021-10-02 criteria provided, single submitter clinical testing Stop-gained (nonsense): predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant (PVS1_VS). It is not observed in the gnomAD v2.1.1 dataset (PM2). The variant has been reported multiple times as pathogenic (ClinVar ID: VCV000095200.3, PS4). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline.
Invitae RCV001854431 SCV002232173 pathogenic Severe neonatal-onset encephalopathy with microcephaly 2021-09-14 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the MECP2 protein in which other variant(s) (p.Tyr450Leufs*37) have been determined to be pathogenic (Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 95200). This premature translational stop signal has been observed in individual(s) with Rett syndrome (PMID: 11005791). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Gln244*) in the MECP2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 243 amino acid(s) of the MECP2 protein.
Centre for Population Genomics, CPG RCV000168689 SCV004232258 pathogenic Rett syndrome 2024-01-09 criteria provided, single submitter curation This variant has been collected from RettBASE and curated to current modified ACMG/AMP criteria. Based on the classification scheme defined by the ClinGen Rett/Angelman-like Expert Panel for Rett/AS-like Disorders Specifications to the ACMG/AMP Variant Interpretation Guidelines VCEP 3.0, this variant is classified as pathogenic. At least the following criteria are met: This variant is absent from gnomAD (PM2_Supporting). Has been observed in at least 5 individuals with phenotypes consistent with MECP2-related disease (PS4). (ClinVar ID 95200, RettBASE, (PMID: 35924478, 28394409, 22982301, 11402105, 15718369) Predicted to result in loss of function, and LOF is a known mechanism of disease (PVS1).
RettBASE RCV000168689 SCV000188211 pathogenic Rett syndrome 2006-02-03 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.