Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000178228 | SCV000230253 | pathogenic | not provided | 2013-11-12 | criteria provided, single submitter | clinical testing | |
Genetic Services Laboratory, |
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, |
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). |
Rett |
RCV000168689 | SCV000188211 | pathogenic | Rett syndrome | 2006-02-03 | no assertion criteria provided | curation |