Submissions for variant NM_020988.3(GNAO1):c.607G>A (p.Gly203Arg)

Total submissions: 14

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000255097	SCV000321737	pathogenic	not provided	2022-01-19	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: 25966631, 23993195, 28973083, 28628939, 28202424, 28688840, 29100083, 30642806, 31780880, 31737037, 34440436, 34122306, 33584783)
Invitae	RCV000468248	SCV000550342	pathogenic	Early infantile epileptic encephalopathy with suppression bursts	2023-07-13	criteria provided, single submitter	clinical testing	This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 203 of the GNAO1 protein (p.Gly203Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Ohtahara syndrome, early infantile epileptic encephalopathy, and movement disorder (PMID: 23993195, 25966631, 26060304, 27072799, 28202424). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 66115). 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. Experimental studies have shown that this missense change affects GNAO1 function (PMID: 28747448). For these reasons, this variant has been classified as Pathogenic.
Institute Of Human Genetics Munich, Klinikum Rechts Der Isar, Tu München	RCV000056408	SCV000680246	pathogenic	Developmental and epileptic encephalopathy, 17	2017-11-08	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV000762963	SCV000893404	pathogenic	Developmental and epileptic encephalopathy, 17; Neurodevelopmental disorder with involuntary movements	2018-10-31	criteria provided, single submitter	clinical testing
Génétique des Maladies du Développement, Hospices Civils de Lyon	RCV000056408	SCV001164237	pathogenic	Developmental and epileptic encephalopathy, 17		criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000255097	SCV001249673	pathogenic	not provided	2020-11-01	criteria provided, single submitter	clinical testing
Kariminejad - Najmabadi Pathology & Genetics Center	RCV001814039	SCV001755204	pathogenic	Abnormality of the nervous system	2021-07-10	criteria provided, single submitter	clinical testing
MGZ Medical Genetics Center	RCV000056408	SCV002580487	pathogenic	Developmental and epileptic encephalopathy, 17	2021-09-24	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV000255097	SCV003826483	pathogenic	not provided	2022-02-02	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003421966	SCV004118582	pathogenic	GNAO1-Related Condition	2022-08-29	criteria provided, single submitter	clinical testing	The GNAO1 c.607G>A variant is predicted to result in the amino acid substitution p.Gly203Arg. This is a recurrent de novo variant reported in individuals with epileptic encephalopathy (Table 1, Nakamura et al. 2013. PubMed ID: 23993195; Arya et al. 2017. PubMed ID: 28202424; Table 1A, Fernández-Marmiesse et al. 2019. PubMed ID: 31780880). 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	RCV000056408	SCV000087517	pathogenic	Developmental and epileptic encephalopathy, 17	2013-09-05	no assertion criteria provided	literature only
Department of Pediatrics, Samsung Medical Center, Samsung Medical Center	RCV001252685	SCV001163828	likely pathogenic	Microcephaly		no assertion criteria provided	research
Service de Génétique Moléculaire, Hôpital Robert Debré	RCV001256978	SCV001433524	pathogenic	Rare genetic intellectual disability		no assertion criteria provided	clinical testing
Pediatric Department, Peking University First Hospital	RCV000762963	SCV001486218	pathogenic	Developmental and epileptic encephalopathy, 17; Neurodevelopmental disorder with involuntary movements	2021-02-03	no assertion criteria provided	clinical testing