NM_020988.3(GNAO1):c.626G>T (p.Arg209Leu) AND Early infantile epileptic encephalopathy with suppression bursts

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jun 15, 2018
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000699557.9

Allele description [Variation Report for NM_020988.3(GNAO1):c.626G>T (p.Arg209Leu)]

NM_020988.3(GNAO1):c.626G>T (p.Arg209Leu)

Gene:

GNAO1:G protein subunit alpha o1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

16q13

Genomic location:

Preferred name:

NM_020988.3(GNAO1):c.626G>T (p.Arg209Leu)

HGVS:

NC_000016.10:g.56336763G>T
NG_042800.1:g.150425G>T
NM_020988.3:c.626G>TMANE SELECT
NM_138736.3:c.626G>T
NP_066268.1:p.Arg209Leu
NP_620073.2:p.Arg209Leu
NC_000016.9:g.56370675G>T
NM_020988.2:c.626G>T
NM_138736.2:c.626G>T

Protein change:

R209L

Links:

dbSNP: rs797044878

NCBI 1000 Genomes Browser:

rs797044878

Molecular consequence:

NM_020988.3:c.626G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_138736.3:c.626G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Early infantile epileptic encephalopathy with suppression bursts (EIEE)
Synonyms:: Early infantile epileptic encephalopathy; Ohtahara syndrome; Developmental and epileptic encephalopathy
Identifiers:: MONDO: MONDO:0100062; MedGen: C0393706; Orphanet: 1934; OMIM: PS308350

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000828273	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jun 15, 2018)	germline	clinical testing	PubMed (8) [See all records that cite these PMIDs] 28357411, 25966631, 28688840, 27864847, 27068059, 26060304, 27625011, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000828273

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jun 15, 2018)

germline

clinical testing

PubMed (8)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

GNAO1 encephalopathy: Broadening the phenotype and evaluating treatment and outcome.

Danti FR, Galosi S, Romani M, Montomoli M, Carss KJ, Raymond FL, Parrini E, Bianchini C, McShane T, Dale RC, Mohammad SS, Shah U, Mahant N, Ng J, McTague A, Samanta R, Vadlamani G, Valente EM, Leuzzi V, Kurian MA, Guerrini R.

Neurol Genet. 2017 Apr;3(2):e143. doi: 10.1212/NXG.0000000000000143.

PubMed [citation]

PMID:: 28357411
PMCID:: PMC5362187

Phenotypic spectrum of GNAO1 variants: epileptic encephalopathy to involuntary movements with severe developmental delay.

Saitsu H, Fukai R, Ben-Zeev B, Sakai Y, Mimaki M, Okamoto N, Suzuki Y, Monden Y, Saito H, Tziperman B, Torio M, Akamine S, Takahashi N, Osaka H, Yamagata T, Nakamura K, Tsurusaki Y, Nakashima M, Miyake N, Shiina M, Ogata K, Matsumoto N.

Eur J Hum Genet. 2016 Jan;24(1):129-34. doi: 10.1038/ejhg.2015.92. Epub 2015 May 13.

PubMed [citation]

PMID:: 25966631
PMCID:: PMC4795232

See all PubMed Citations (8)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000828273.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (8)

Description

For these reasons, this variant has been classified as Pathogenic. 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. 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. This variant has been observed to be de novo in an individual with developmental delay and a movement disorder (PMID:¬†27625011). This variant is not present in population databases (ExAC no frequency). 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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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