Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000190691 | SCV000244132 | pathogenic | Inborn genetic diseases | 2016-06-06 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000255659 | SCV000321738 | pathogenic | not provided | 2022-12-08 | criteria provided, single submitter | clinical testing | Published functional studies demonstrate that R209H knock-in mice display similar phenotype to patients harboring this variant and respond to risperidone, an approved pharmacological agent (Larrivee et al., 2020); Not observed at significant frequency in large population cohorts (gnomAD); 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: 31907305, 26060304, 27625011, 27068059, 30682224, 33298085, 33084218, 33098801, 33258288, 28688840, 28357411, 27864847, 25966631, 28747448, 30838255, 33619735) |
Institute Of Human Genetics Munich, |
RCV000490633 | SCV001150118 | pathogenic | Neurodevelopmental disorder with involuntary movements | 2018-03-20 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001065368 | SCV001230324 | pathogenic | Early infantile epileptic encephalopathy with suppression bursts | 2023-10-25 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 209 of the GNAO1 protein (p.Arg209His). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with neurodevelopmental disorder with involuntary movements (NEDIM) (PMID: 26060304, 27068059, 27625011). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 208677). 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 with a positive predictive value of 95%. This variant disrupts the p.Arg209 amino acid residue in GNAO1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 25966631, 27625011, 27864847, 28357411, 28688840). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |
Revvity Omics, |
RCV000255659 | SCV002024862 | pathogenic | not provided | 2021-06-14 | criteria provided, single submitter | clinical testing | |
3billion | RCV000490633 | SCV002058662 | pathogenic | Neurodevelopmental disorder with involuntary movements | 2022-01-03 | criteria provided, single submitter | clinical testing | The variant has been previously reported as de novo in a similarly affected individual (PMID: 27068059, PS2_S). Same nucleotide change resulting in same amino acid change has been previously reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000208677, PS1_S). A different missense change at the same codon has been reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000265350,VCV000431699, PM5_M). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.914, 3CNET: 0.917, PP3_P). A missense variant is a common mechanism associated with Neurodevelopmental disorder with involuntary movements (PP2_P). It is not observed in the gnomAD v2.1.1 dataset (PM2_M). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline. |
OMIM | RCV000490633 | SCV000579319 | pathogenic | Neurodevelopmental disorder with involuntary movements | 2017-06-02 | no assertion criteria provided | literature only |