Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002019308 | SCV002282276 | likely pathogenic | Developmental and epileptic encephalopathy, 2; Angelman syndrome-like | 2022-05-27 | criteria provided, single submitter | clinical testing | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt CDKL5 protein function. This missense change has been observed in individuals with atypical Rett syndrome and/or CDKL5-related conditions (PMID: 27265524, 33436160). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 177 of the CDKL5 protein (p.Tyr177Cys). |
| Mendelics | RCV002246646 | SCV002516250 | likely pathogenic | Developmental and epileptic encephalopathy, 2 | 2022-05-04 | criteria provided, single submitter | clinical testing | |
| Centre for Population Genomics, |
RCV004729023 | SCV005335130 | uncertain significance | CDKL5 disorder | 2024-09-05 | 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 variant of uncertain significance. At least the following criteria are met: Has been observed in at least 3 individuals with phenotypes consistent with CDKL5 disorder (PS4_Moderate, PMID: 27265524, PMID: 33436160, ClinVar Variation ID: 1496916). Computational prediction analysis tools suggests a deleterious impact (REVEL score>= 0.75) (PP3). This variant is absent from gnomAD (PM2_Supporting). Well-established in vitro or in vivo functional studies supportive of a damaging effect on the protein function (PS3_supporting, PMID: 27265524). |