ClinVar Miner

Submissions for variant NM_020988.3(GNAO1):c.680C>T (p.Ala227Val) (rs797045599)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000193275 SCV000247487 likely pathogenic Early infantile epileptic encephalopathy 17 2015-05-22 criteria provided, single submitter clinical testing
GeneDx RCV000493045 SCV000582587 pathogenic not provided 2016-06-02 criteria provided, single submitter clinical testing The A227V pathogenic variant in the GNAO1 gene has been reported previously as an assumed denovo change in an individual with early-onset epileptic encephalopathy (Saitsu et al., 2015). TheA227V variant was not observed in approximately 6500 individuals of European and AfricanAmerican ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benignvariant in these populations. The A227V variant is a conservative amino acid substitution, which isnot likely to impact secondary protein structure as these residues share similar properties. Thissubstitution occurs at a position that is conserved across species. In silico analysis predicts this variantis probably damaging to the protein structure/function. We interpret A227V as a pathogenic variant.
Invitae RCV000694174 SCV000822605 pathogenic Early infantile epileptic encephalopathy 2018-04-16 criteria provided, single submitter clinical testing This sequence change replaces alanine with valine at codon 227 of the GNAO1 protein (p.Ala227Val). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and valine. This variant is not present in population databases (ExAC no frequency). This variant has been reported to be de novo in an individual affected with early onset epileptic encephalopathy (PMID: 25966631). ClinVar contains an entry for this variant (Variation ID: 211088). Experimental studies have shown that this missense change showed a partial loss of function with an intermediate effect in cAMP production  (PMID: 28747448). For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics,Fulgent Genetics RCV000762964 SCV000893405 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 RCV000193275 SCV001164114 pathogenic Early infantile epileptic encephalopathy 17 2016-06-21 criteria provided, single submitter clinical testing

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