ClinVar Miner

Submissions for variant NM_020988.3(GNAO1):c.709G>A (p.Glu237Lys)

dbSNP: rs1064794533
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx 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, 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, University Hospital TU Dresden, University Hospital TU Dresden 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, University of Cambridge RCV001003613 SCV001162024 likely pathogenic Dyskinesia; Chorea no assertion criteria provided research

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