Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001300092 | SCV001489216 | pathogenic | Epilepsy, childhood absence, susceptibility to, 1; Epilepsy, childhood absence, susceptibility to, 5 | 2020-11-03 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine with arginine at codon 304 of the GABRB3 protein (p.Lys304Arg). The lysine residue is highly conserved and there is a small physicochemical difference between lysine and arginine. For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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 GABRB3 protein function. This variant has been observed in individual(s) with clinical features of developmental and epileptic encephalopathy (Invitae). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (ExAC no frequency). |
| Equipe Genetique des Anomalies du Developpement, |
RCV001358688 | SCV001554498 | likely pathogenic | Developmental and epileptic encephalopathy, 43 | criteria provided, single submitter | clinical testing |