ClinVar Miner

Submissions for variant NM_020988.3(GNAO1):c.626G>T (p.Arg209Leu) (rs797044878)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
TIDEX, University of British Columbia RCV000655933 SCV000586815 likely pathogenic Early infantile epileptic encephalopathy 17 criteria provided, single submitter research
Invitae RCV000699557 SCV000828273 pathogenic Early infantile epileptic encephalopathy with suppression bursts 2018-07-03 criteria provided, single submitter clinical testing This sequence change replaces arginine with leucine at codon 209 of the GNAO1 protein (p.Arg209Leu). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and leucine. This variant is not present in population databases (ExAC no frequency). This variant has been observed to be de novo in an individual with developmental delay and a movement disorder (PMID: 27625011). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. Variants that disrupt the p.Arg209 amino acid residue in GNAO1 have been observed in affected individuals (PMID: 28357411, 25966631, 28688840, 27864847, 27068059, 26060304, 27625011). This suggests that it is a clinically significant residue, and that other variants that disrupt this residue are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.

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