Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV000133056 | SCV001712020 | pathogenic | Rett syndrome | 2021-03-26 | reviewed by expert panel | curation | The p.Pro101Ser variant has been observed in at least 4 other individuals with Rett syndrome (RettBASE, internal database) (PS4). Multiple pathogenic missense variants have been previously identified within this codon which indicates that this residue is critical to the function of the protein (PMID 10767337, 31439979) (PM5_Strong). The p.Pro101Ser variant in MECP2 is absent from gnomAD (PM2_Supporting). Computational prediction analysis tools suggests a deleterious impact; however, this information does not predict clinical significance on its own (PP3). The p.Pro101Ser variant in MECP2 has been reported in an individual with a clinical phenotype suggestive of Rett syndrome (PMID 11269512) (PP4). In summary, the p.Pro101Ser variant in MECP2 is classified as pathogenic for Rett syndrome based on the ACMG/AMP criteria (PS4, PM5_strong, PM2_supporting, PP3, PP4). |
Genetic Services Laboratory, |
RCV000133056 | SCV000595741 | pathogenic | Rett syndrome | 2016-08-24 | criteria provided, single submitter | clinical testing | |
Centre for Population Genomics, |
RCV000133056 | SCV004101601 | likely pathogenic | Rett syndrome | 2023-10-12 | 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 likely pathogenic. At least the following criteria are met: Occurs in the well-characterized Methyl-DNA binding (MDB) functional domain of MECP2 (PM1). This variant is absent from gnomAD (PM2_Supporting). This variant has been identified as a de novo occurrence in an individual with Rett syndrome without confirmation of paternity and maternity (PM6, PMID: 11269512). Has been observed in at least 3 individuals with phenotypes consistent with MECP2-related disease (PS4_Moderate, RettBASE internal database). Computational prediction analysis tools suggests a deleterious impact (REVEL score >=0.75) (PP3). |
Rett |
RCV000133056 | SCV000188044 | uncertain significance | Rett syndrome | 2006-02-03 | no assertion criteria provided | curation |