Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clinical Molecular Genetics Laboratory, |
RCV000132985 | SCV000778314 | pathogenic | Rett syndrome | 2018-06-01 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000690876 | SCV000818605 | pathogenic | Severe neonatal-onset encephalopathy with microcephaly | 2023-10-06 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gln437Alafs*49) in the MECP2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 50 amino acid(s) of the MECP2 protein. This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with Rett syndrome (PMID: 11055898; Invitae). This variant is also known as c.1308delTC and c.1308_1309del2. ClinVar contains an entry for this variant (Variation ID: 143457). This variant disrupts a region of the MECP2 protein in which other variant(s) (p.Ala439Glyfs*47, p.Tyr450Leufs*37) have been determined to be pathogenic (PMID: 10814718, 16473305, 19914908, 23696494). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |
Centre for Population Genomics, |
RCV000132985 | SCV004098741 | pathogenic | Rett syndrome | 2023-08-14 | 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 2.0, this variant is classified as pathogenic. At least the following criteria are met: Predicted to result in loss of function, and LOF is a known mechanism of disease (PVS1). This variant is absent from gnomAD (PM2_Supporting).It has been observed in at least 2 individuals with phenotypes consistent with MECP2-related disease (PS4_Supporting, PMID: 11055898, RettBase internal database). |
Rett |
RCV000132985 | SCV000187969 | pathogenic | Rett syndrome | 2002-04-10 | no assertion criteria provided | curation |