Total submissions: 9
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Genetic Services Laboratory, |
RCV000133290 | SCV000248006 | pathogenic | Rett syndrome | 2013-02-08 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000256087 | SCV000322254 | pathogenic | not provided | 2021-03-30 | criteria provided, single submitter | clinical testing | Not observed in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function; Published functional studies demonstrate that the p.R306H variant abolishes binding of MECP2 to DNA (Heckman et al., 2014); This variant is associated with the following publications: (PMID: 31780880, 11055898, 12655490, 11214906, 15057977, 16473305, 24970834, 10767337, 23921973) |
Molecular Diagnostics Lab, |
RCV000133290 | SCV000537171 | likely pathogenic | Rett syndrome | 2015-06-30 | criteria provided, single submitter | clinical testing | |
Neuro |
RCV000133290 | SCV000693793 | likely pathogenic | Rett syndrome | 2018-01-01 | criteria provided, single submitter | clinical testing | |
Laboratory of Molecular Genetics |
RCV001778753 | SCV002016294 | pathogenic | Neurodevelopmental disorder | 2021-08-31 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV001857484 | SCV002120295 | pathogenic | Severe neonatal-onset encephalopathy with microcephaly | 2022-12-14 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Arg306 amino acid residue in MECP2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 10991688, 14649554, 16473305, 23770565, 24511209, 24970834). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. ClinVar contains an entry for this variant (Variation ID: 143746). This missense change has been observed in individual(s) with Rett syndrome (PMID: 10767337, 23921973). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 306 of the MECP2 protein (p.Arg306His). |
Centre for Population Genomics, |
RCV000133290 | SCV004232314 | pathogenic | Rett syndrome | 2023-12-06 | 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). Computational prediction analysis tools suggests a deleterious impact (REVEL score>= 0.75) (PP3). Has been observed in at least 5 individuals with phenotypes consistent with MECP2-related disease (PS4).This variant has been identified as a de novo occurrence in at least 2 individuals with Rett syndrome, without confirmation of paternity and maternity (PM6_Strong).(PubMed: 11055898‚ 15057977‚ 16473305, 10767337, 23921973 ClinVar database Variation ID: 143746) |
Rett |
RCV000133290 | SCV000188299 | pathogenic | Rett syndrome | 2011-02-15 | no assertion criteria provided | curation | |
Laboratory of Medical Genetics, |
RCV000133290 | SCV002583294 | pathogenic | Rett syndrome | 2022-10-09 | no assertion criteria provided | research |