Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Neuro |
RCV000585869 | SCV000693764 | likely pathogenic | Developmental and epileptic encephalopathy, 2 | 2018-01-01 | criteria provided, single submitter | clinical testing | |
Invitae | RCV002530871 | SCV002953859 | pathogenic | Developmental and epileptic encephalopathy, 2; Angelman syndrome-like | 2022-09-20 | criteria provided, single submitter | clinical testing | This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 152 of the CDKL5 protein (p.Cys152Tyr). This variant is not present in population databases (gnomAD no frequency). For these reasons, this variant has been classified as 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. ClinVar contains an entry for this variant (Variation ID: 495236). This missense change has been observed in individual(s) with clinical features of CDKL5-related conditions (PMID: 31780880). In at least one individual the variant was observed to be de novo. |