ClinVar Miner

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

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000255097 SCV000321737 pathogenic not provided 2017-04-07 criteria provided, single submitter clinical testing The G203R variant in the GNAO1 gene has been reported previously in association with epileptic encephalopathy with movement disorders (Nakamura et al., 2013; Saitsu et al., 2015). In addition, this variant has been observed as a de novo finding with confirmed parentage in several individuals referred for testing at GeneDx with features of a GNAO1-related disorder. This variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The G203R variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret G203R as a pathogenic variant.
Invitae RCV000468248 SCV000550342 pathogenic Early infantile epileptic encephalopathy with suppression bursts 2020-01-23 criteria provided, single submitter clinical testing This sequence change replaces glycine with arginine at codon 203 of the GNAO1 protein (p.Gly203Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is not present in population databases (rs587777057, ExAC no frequency). This variant has been shown to arise de novo in individuals affected with Ohtahara syndrome (PMID: 23993195) and in individuals affected with early infantile epileptic encephalopathy and movement disorder (PMID: 25966631, 27072799, 28202424, 26060304). Experimental studies in vitro have shown that this missense change results in gain-of-function GNAO1 activity with regards to a2A adrenergic receptor-mediated inhibition of cAMP (PMID: 28747448). For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics,Fulgent Genetics RCV000762963 SCV000893404 pathogenic Early infantile 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 Early infantile epileptic encephalopathy 17 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000255097 SCV001249673 pathogenic not provided 2020-11-01 criteria provided, single submitter clinical testing
OMIM RCV000056408 SCV000087517 pathogenic Early infantile epileptic encephalopathy 17 2013-09-05 no assertion criteria provided literature only
Institute of Human Genetics, Klinikum rechts der Isar RCV000056408 SCV000680246 pathogenic Early infantile epileptic encephalopathy 17 2017-11-08 no assertion criteria provided clinical testing
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 Early infantile epileptic encephalopathy 17; Neurodevelopmental disorder with involuntary movements 2021-02-03 no assertion criteria provided clinical testing

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