Total submissions: 12
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000256155 | SCV000322148 | pathogenic | not provided | 2022-01-28 | criteria provided, single submitter | clinical testing | 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: 28688840, 28357411, 25966631, 27864847, 28747448, 28628939, 27916449, 25533962, 30682224, 28191890, 28668776, 30642806, 31190250, 32581362, 33446253, 33098801, 33358199, 33619735) |
Invitae | RCV000475848 | SCV000550340 | pathogenic | Early infantile epileptic encephalopathy with suppression bursts | 2023-11-20 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 209 of the GNAO1 protein (p.Arg209Cys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with early infantile epileptic encephalopathy (PMID: 25966631, 27864847, 28357411, 28688840). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 265350). 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: 26060304, 27068059, 27625011). 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. |
Ambry Genetics | RCV000622320 | SCV000740968 | pathogenic | Inborn genetic diseases | 2015-10-07 | criteria provided, single submitter | clinical testing | |
Institute Of Human Genetics Munich, |
RCV000490628 | SCV001149794 | pathogenic | Neurodevelopmental disorder with involuntary movements | 2020-08-17 | criteria provided, single submitter | clinical testing | |
Ce |
RCV000256155 | SCV001249674 | pathogenic | not provided | 2019-01-01 | criteria provided, single submitter | clinical testing | |
Institute of Medical Genetics and Applied Genomics, |
RCV000256155 | SCV001446487 | pathogenic | not provided | 2020-10-23 | criteria provided, single submitter | clinical testing | |
Knight Diagnostic Laboratories, |
RCV000490628 | SCV001449009 | pathogenic | Neurodevelopmental disorder with involuntary movements | 2019-01-18 | criteria provided, single submitter | clinical testing | |
Baylor Genetics | RCV000490628 | SCV001529933 | pathogenic | Neurodevelopmental disorder with involuntary movements | 2018-08-13 | criteria provided, single submitter | clinical testing | This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. This variant has been previously in multiple individuals with intellectual disability, developmental delay, and movement disorders [PMID 25966631, 28357411, 28688840, 27864847, 27916449] |
3billion | RCV001775107 | SCV002012060 | pathogenic | Developmental and epileptic encephalopathy, 17 | 2021-10-02 | criteria provided, single submitter | clinical testing | Same nucleotide change resulting in same amino acid change has been previously reported multiple times as de novo in similarly affected indivisual (PMID: 25533962, 28688840 PS2, PS4). The missense variant is located in a mutational hot spot and/or well-established functional domain in which established pathogenic variants have been reported (PM1). It is not observed in the gnomAD v2.1.1 dataset (PM2). A different missense change at the same codon (p.Arg209Leu and Arg209His) has been reported as pathogenic (VCV000431699.1, VCV000208677.6, PM5). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.888, 3Cnet: 0.960, PP3). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline. |
Preventiongenetics, |
RCV003401217 | SCV004111018 | pathogenic | GNAO1-Related Condition | 2023-04-10 | criteria provided, single submitter | clinical testing | The GNAO1 c.625C>T variant is predicted to result in the amino acid substitution p.Arg209Cys. This variant has been reported as de novo in multiple individuals with intellectual disability, developmental delay, and movement disorders (Saitsu. 2016. PubMed ID: 25966631; Brunet. 2021. PubMed ID: 33619735; Evers. 2017. PubMed ID: 28688840; Kelly. 2019. PubMed ID: 30682224; Malaquias. 2019. PubMed ID: 31190250). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. This variant is interpreted as pathogenic. |
OMIM | RCV000490628 | SCV000579320 | pathogenic | Neurodevelopmental disorder with involuntary movements | 2017-06-02 | no assertion criteria provided | literature only | |
NIHR Bioresource Rare Diseases, |
RCV001003612 | SCV001162023 | likely pathogenic | Movement disorder | no assertion criteria provided | research |