Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000477989 | SCV000569391 | pathogenic | not provided | 2021-11-11 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 29389947, 30103967, 31737037, 31130284, 33098801, 32581362, 31780880, 30642806, 29935962, 28668776) |
Fulgent Genetics, |
RCV000762965 | SCV000893406 | likely pathogenic | Developmental and epileptic encephalopathy, 17; Neurodevelopmental disorder with involuntary movements | 2018-10-31 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001851189 | SCV002234284 | pathogenic | Early infantile epileptic encephalopathy with suppression bursts | 2021-08-24 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid with lysine at codon 237 of the GNAO1 protein (p.Glu237Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is not present in population databases (ExAC 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 GNAO1 protein function. ClinVar contains an entry for this variant (Variation ID: 420523). This variant has been observed in individual(s) with clinical features of GNAO1-related conditions (PMID: 28668776, 29389947, 29935962, 30642806, 31130284, 31737037, 31780880, 32581362). In at least one individual the variant was observed to be de novo. |
Institute for Clinical Genetics, |
RCV000477989 | SCV004026092 | likely pathogenic | not provided | 2022-07-11 | criteria provided, single submitter | clinical testing | PS2, PS4_MOD, PP3, PP2, PM2_SUP |
NIHR Bioresource Rare Diseases, |
RCV001003613 | SCV001162024 | likely pathogenic | Dyskinesia; Chorea | no assertion criteria provided | research |