Cells transfected with the E246K variant exhibited lower protein levels compared to wild-type, and functional studies demonstrated a gain-of-function effect for the E246K variant (PMID: 28747448); Not observed at significant frequency in large population cohorts (gnomAD); 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: 31076915, 27068059, 25356970, 26795593, 25966631, 28688840, 28628939, 29761117, 28668776, 33298085, 34122306, 28747448)
ClinVar Genomic variation as it relates to human health
NM_020988.3(GNAO1):c.736G>A (p.Glu246Lys)
Germline
Classification
Help
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
(11)
Help
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
Pathogenic
11
criteria provided, multiple submitters, no conflicts
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_020988.3(GNAO1):c.736G>A (p.Glu246Lys)
Variation ID: 208777 Accession: VCV000208777.37
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 16q13 16: 56351396 (GRCh38) [ NCBI UCSC ] 16: 56385308 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Jun 5, 2017 Sep 16, 2024 Dec 26, 2023 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_020988.3:c.736G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_066268.1:p.Glu246Lys missense NC_000016.10:g.56351396G>A NC_000016.9:g.56385308G>A NG_042800.1:g.165058G>A P09471:p.Glu246Lys - Protein change
- E246K
- Other names
- -
- Canonical SPDI
- NC_000016.10:56351395:G:A
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- -
-
Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
- -
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
- -
- Links
Genes
| Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
|---|---|---|---|---|---|---|
| HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
|||
| GNAO1 | Little evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
482 | 522 | |
Conditions - Germline
| Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
|---|---|---|---|---|
| Pathogenic (1) |
criteria provided, single submitter
|
Jun 6, 2014 | RCV000190803.5 | |
| Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
|
Oct 5, 2020 | RCV000490631.5 | |
| Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
|
Dec 26, 2023 | RCV000254701.8 | |
| Pathogenic (1) |
criteria provided, single submitter
|
Jul 10, 2021 | RCV001814097.2 | |
| Pathogenic (1) |
criteria provided, single submitter
|
Oct 24, 2022 | RCV001857676.5 | |
| Pathogenic (1) |
criteria provided, single submitter
|
Jan 3, 2022 | RCV001808530.2 | |
| Pathogenic (1) |
no assertion criteria provided
|
Feb 3, 2021 | RCV001580372.2 | |
| Pathogenic (1) |
criteria provided, single submitter
|
May 10, 2020 | RCV003996903.1 |
Submissions - Germline
| Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
|
|---|---|---|---|---|---|
|
Pathogenic
(Jun 06, 2014)
|
criteria provided, single submitter
Method: clinical testing
|
Inborn genetic diseases
Affected status: yes
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000244244.7
First in ClinVar: Sep 14, 2015 Last updated: Jan 07, 2023 |
Observation 1:
Number of individuals with the variant: 1
Clinical Features:
Global developmental delay (present) , Muscular hypotonia (present) , Movement disorder (present) , Chorea (present) , Myoclonus (present) , Neurodevelopmental delay (present) , Drooling (present) … (more)
Global developmental delay (present) , Muscular hypotonia (present) , Movement disorder (present) , Chorea (present) , Myoclonus (present) , Neurodevelopmental delay (present) , Drooling (present) , Open mouth (present) , Abnormal size of the palpebral fissures (present) , Long eyelashes (present) , Epicanthus (present) , Coarse facial features (present) , Widely spaced teeth (present) (less)
Sex: female
Ethnicity/Population group: Caucasian
Observation 2:
Number of individuals with the variant: 1
Sex: male
Observation 3:
Number of individuals with the variant: 1
Clinical Features:
Decreased muscle mass (present) , Abnormal muscle tone (present) , Motor delay (present) , Delayed speech and language development (present) , Paroxysmal choreoathetosis (present) , … (more)
Decreased muscle mass (present) , Abnormal muscle tone (present) , Motor delay (present) , Delayed speech and language development (present) , Paroxysmal choreoathetosis (present) , Slowly progressive spastic quadriparesis (present) (less)
Sex: male
Ethnicity/Population group: Caucasian
|
|
|
Pathogenic
(Dec 26, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000321739.8
First in ClinVar: Oct 09, 2016 Last updated: Sep 16, 2024 |
Comment:
Cells transfected with the E246K variant exhibited lower protein levels compared to wild-type, and functional studies demonstrated a gain-of-function effect for the E246K variant (PMID: … (more)
Cells transfected with the E246K variant exhibited lower protein levels compared to wild-type, and functional studies demonstrated a gain-of-function effect for the E246K variant (PMID: 28747448); Not observed at significant frequency in large population cohorts (gnomAD); 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: 31076915, 27068059, 25356970, 26795593, 25966631, 28688840, 28628939, 29761117, 28668776, 33298085, 34122306, 28747448) (less)
|
|
|
Pathogenic
(Oct 23, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
(Autosomal unknown)
Affected status: yes
Allele origin:
germline
|
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen
Accession: SCV001446748.1
First in ClinVar: Nov 28, 2020 Last updated: Nov 28, 2020 |
Clinical Features:
Global developmental delay (present) , Hemiparesis (present) , Developmental regression (present) , Infantile axial hypotonia (present)
Sex: female
|
|
|
Pathogenic
(Jul 10, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Abnormality of the nervous system
Affected status: yes
Allele origin:
de novo
|
Kariminejad - Najmabadi Pathology & Genetics Center
Accession: SCV001755297.1
First in ClinVar: Jan 22, 2022 Last updated: Jan 22, 2022 |
|
|
|
Pathogenic
(Jan 03, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Developmental and epileptic encephalopathy, 17
Affected status: yes
Allele origin:
germline
|
3billion
Accession: SCV002058168.1
First in ClinVar: Jan 15, 2022 Last updated: Jan 15, 2022 |
Comment:
The variant has been previously reported as de novo in a similarly affected individual (PMID: 27068059, PS2_S). Same nucleotide change resulting in same amino acid … (more)
The variant has been previously reported as de novo in a similarly affected individual (PMID: 27068059, PS2_S). Same nucleotide change resulting in same amino acid change has been previously reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000208777, PMID:25966631, PS1_S). A different missense change at the same codon (p.Glu246Gln, p.Glu246Gly) has been reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000689763, PMID:28357411, PMID:31216405, PM5_M). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.844, 3CNET: 0.848, PP3_P). A missense variant is a common mechanism associated with Epileptic encephalopathy (PP2_P). It is not observed in the gnomAD v2.1.1 dataset (PM2_M). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline. (less)
Clinical Features:
Clinodactyly of the 5th finger (present) , Generalized hypotonia (present) , Global developmental delay (present) , High palate (present) , Inspiratory stridor (present)
|
|
|
Pathogenic
(-)
|
criteria provided, single submitter
Method: clinical testing
|
Neurodevelopmental disorder with involuntary movements
Affected status: yes
Allele origin:
germline
|
Institute of Human Genetics, Clinical Exome/Genome Diagnostics Group, University Hospital Bonn
Accession: SCV002822904.1
First in ClinVar: Jan 21, 2023 Last updated: Jan 21, 2023 |
|
|
|
Pathogenic
(Oct 24, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Early infantile epileptic encephalopathy with suppression bursts
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV002241963.3
First in ClinVar: Mar 28, 2022 Last updated: Feb 14, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects GNAO1 function (PMID: 28747448). Advanced modeling … (more)
For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects GNAO1 function (PMID: 28747448). 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: 208777). This missense change has been observed in individual(s) with neurodevelopmental disorder with involuntary movements (PMID: 27068059). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 246 of the GNAO1 protein (p.Glu246Lys). (less)
|
|
|
Pathogenic
(Oct 05, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
Neurodevelopmental disorder with involuntary movements
Affected status: unknown
Allele origin:
unknown
|
Illumina Laboratory Services, Illumina
Accession: SCV004801504.1
First in ClinVar: Mar 23, 2024 Last updated: Mar 23, 2024 |
Comment:
The GNAO1 c.736G>A p.(Glu246Lys) missense variant has been identified in individuals with a phenotype consistent with neurodevelopmental disorder with involuntary movements, in whom the variant … (more)
The GNAO1 c.736G>A p.(Glu246Lys) missense variant has been identified in individuals with a phenotype consistent with neurodevelopmental disorder with involuntary movements, in whom the variant occurred in a de novo state in at least four individuals (Feng et al. 2018).This variant is not observed in version 2.1.1 of the Genome Aggregation Database. Functional studies demonstrated when the p.Glu246Lys variant was expressed in HEK293T cells, it exhibited increased potency for α2A AR–mediated cAMP inhibition consistent with a gain-of-function mechanism (Feng et al. 2017). Multiple lines of computational evidence suggest the variant may impact the gene or gene product. The variant was identified in a de novo state in the proband. Based on the collective evidence the c.736G>A p.(Glu246Lys) variant is classified as pathogenic for neurodevelopmental disorder with involuntary movements. (less)
|
|
|
Pathogenic
(May 10, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
GNAO1-related developmental delay-seizures-movement disorder spectrum
Affected status: unknown
Allele origin:
unknown
|
Illumina Laboratory Services, Illumina
Accession: SCV004814153.1
First in ClinVar: Apr 20, 2024 Last updated: Apr 20, 2024 |
Comment:
The GNAO1 c.736G>A p.(Glu246Lys) missense variant has been identified in individuals with a phenotype consistent with GNAO1-related developmental delay-seizures-movement disorder spectrum. The variant occurred de … (more)
The GNAO1 c.736G>A p.(Glu246Lys) missense variant has been identified in individuals with a phenotype consistent with GNAO1-related developmental delay-seizures-movement disorder spectrum. The variant occurred de novo in at least four of the individuals (Feng et al. 2018). This variant is not observed in version 2.1.1 of the Genome Aggregation Database. Functional studies found that when the p.Glu246Lys variant expressed in HEK293T cells, it exhibited increased potency for alpha-2A AR-mediated cAMP inhibition consistent with a gain-of-function mechanism (Feng et al. 2017). Multiple lines of computational evidence suggest the variant may impact the gene or gene product. The variant was identified in a de novo state in the proband. Based on the collective evidence the c.736G>A p.(Glu246Lys) variant is classified as pathogenic for GNAO1-related developmental delay-seizures-movement disorder spectrum. (less)
|
|
|
Pathogenic
(Jun 02, 2017)
|
no assertion criteria provided
Method: literature only
|
NEURODEVELOPMENTAL DISORDER WITH INVOLUNTARY MOVEMENTS
Affected status: not provided
Allele origin:
germline
|
OMIM
Accession: SCV000579321.1
First in ClinVar: Jun 05, 2017 Last updated: Jun 05, 2017 |
Comment on evidence:
In a 13-year-old girl with neurodevelopmental disorder with involuntary movements (NEDIM; 617493), Saitsu et al. (2016) identified a de novo heterozygous c.736G-A transition (c.736G-A, NM_020988.2) … (more)
In a 13-year-old girl with neurodevelopmental disorder with involuntary movements (NEDIM; 617493), Saitsu et al. (2016) identified a de novo heterozygous c.736G-A transition (c.736G-A, NM_020988.2) in exon 7 of the GNAO1 gene, resulting in a glu246-to-lys (E246K) substitution at a highly conserved residue. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, was not found in the Exome Variant Server database or in 575 in-house control exomes. Functional studies of the variant and studies of patient cells were not performed, but molecular modeling predicted that the mutation would destabilize the G-alpha-containing complexes mainly in GTP-bound active state. In 4 patients, including 2 sibs, with NEDIM, Ananth et al. (2016) identified a de novo heterozygous E246K mutation. The mutations were found by whole-exome sequencing. Functional studies of the variants and studies of patient cells were not performed. (less)
|
|
|
Pathogenic
(Feb 03, 2021)
|
no assertion criteria provided
Method: clinical testing
|
Developmental delay
Affected status: yes
Allele origin:
de novo
|
Pediatric Department, Peking University First Hospital
Accession: SCV001486219.1
First in ClinVar: Aug 27, 2021 Last updated: Aug 27, 2021 |
Age: 0-9 years
Sex: male
|
|
| click to load more click to collapse | |||||
Comment:
Comment:
The variant has been previously reported as de novo in a similarly affected individual (PMID: 27068059, PS2_S). Same nucleotide change resulting in same amino acid change has been previously reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000208777, PMID:25966631, PS1_S). A different missense change at the same codon (p.Glu246Gln, p.Glu246Gly) has been reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000689763, PMID:28357411, PMID:31216405, PM5_M). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.844, 3CNET: 0.848, PP3_P). A missense variant is a common mechanism associated with Epileptic encephalopathy (PP2_P). It is not observed in the gnomAD v2.1.1 dataset (PM2_M). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline.
Comment:
For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects GNAO1 function (PMID: 28747448). 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: 208777). This missense change has been observed in individual(s) with neurodevelopmental disorder with involuntary movements (PMID: 27068059). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 246 of the GNAO1 protein (p.Glu246Lys).
Comment:
The GNAO1 c.736G>A p.(Glu246Lys) missense variant has been identified in individuals with a phenotype consistent with neurodevelopmental disorder with involuntary movements, in whom the variant occurred in a de novo state in at least four individuals (Feng et al. 2018).This variant is not observed in version 2.1.1 of the Genome Aggregation Database. Functional studies demonstrated when the p.Glu246Lys variant was expressed in HEK293T cells, it exhibited increased potency for α2A AR–mediated cAMP inhibition consistent with a gain-of-function mechanism (Feng et al. 2017). Multiple lines of computational evidence suggest the variant may impact the gene or gene product. The variant was identified in a de novo state in the proband. Based on the collective evidence the c.736G>A p.(Glu246Lys) variant is classified as pathogenic for neurodevelopmental disorder with involuntary movements.
Comment:
The GNAO1 c.736G>A p.(Glu246Lys) missense variant has been identified in individuals with a phenotype consistent with GNAO1-related developmental delay-seizures-movement disorder spectrum. The variant occurred de novo in at least four of the individuals (Feng et al. 2018). This variant is not observed in version 2.1.1 of the Genome Aggregation Database. Functional studies found that when the p.Glu246Lys variant expressed in HEK293T cells, it exhibited increased potency for alpha-2A AR-mediated cAMP inhibition consistent with a gain-of-function mechanism (Feng et al. 2017). Multiple lines of computational evidence suggest the variant may impact the gene or gene product. The variant was identified in a de novo state in the proband. Based on the collective evidence the c.736G>A p.(Glu246Lys) variant is classified as pathogenic for GNAO1-related developmental delay-seizures-movement disorder spectrum.
Germline Functional Evidence
| There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Comment:
Cells transfected with the E246K variant exhibited lower protein levels compared to wild-type, and functional studies demonstrated a gain-of-function effect for the E246K variant (PMID: 28747448); Not observed at significant frequency in large population cohorts (gnomAD); 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: 31076915, 27068059, 25356970, 26795593, 25966631, 28688840, 28628939, 29761117, 28668776, 33298085, 34122306, 28747448)
Comment:
The variant has been previously reported as de novo in a similarly affected individual (PMID: 27068059, PS2_S). Same nucleotide change resulting in same amino acid change has been previously reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000208777, PMID:25966631, PS1_S). A different missense change at the same codon (p.Glu246Gln, p.Glu246Gly) has been reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000689763, PMID:28357411, PMID:31216405, PM5_M). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.844, 3CNET: 0.848, PP3_P). A missense variant is a common mechanism associated with Epileptic encephalopathy (PP2_P). It is not observed in the gnomAD v2.1.1 dataset (PM2_M). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline.
Comment:
For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects GNAO1 function (PMID: 28747448). 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: 208777). This missense change has been observed in individual(s) with neurodevelopmental disorder with involuntary movements (PMID: 27068059). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 246 of the GNAO1 protein (p.Glu246Lys).
Comment:
The GNAO1 c.736G>A p.(Glu246Lys) missense variant has been identified in individuals with a phenotype consistent with neurodevelopmental disorder with involuntary movements, in whom the variant occurred in a de novo state in at least four individuals (Feng et al. 2018).This variant is not observed in version 2.1.1 of the Genome Aggregation Database. Functional studies demonstrated when the p.Glu246Lys variant was expressed in HEK293T cells, it exhibited increased potency for α2A AR–mediated cAMP inhibition consistent with a gain-of-function mechanism (Feng et al. 2017). Multiple lines of computational evidence suggest the variant may impact the gene or gene product. The variant was identified in a de novo state in the proband. Based on the collective evidence the c.736G>A p.(Glu246Lys) variant is classified as pathogenic for neurodevelopmental disorder with involuntary movements.
Comment:
The GNAO1 c.736G>A p.(Glu246Lys) missense variant has been identified in individuals with a phenotype consistent with GNAO1-related developmental delay-seizures-movement disorder spectrum. The variant occurred de novo in at least four of the individuals (Feng et al. 2018). This variant is not observed in version 2.1.1 of the Genome Aggregation Database. Functional studies found that when the p.Glu246Lys variant expressed in HEK293T cells, it exhibited increased potency for alpha-2A AR-mediated cAMP inhibition consistent with a gain-of-function mechanism (Feng et al. 2017). Multiple lines of computational evidence suggest the variant may impact the gene or gene product. The variant was identified in a de novo state in the proband. Based on the collective evidence the c.736G>A p.(Glu246Lys) variant is classified as pathogenic for GNAO1-related developmental delay-seizures-movement disorder spectrum.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Spectrum of movement disorders in GNAO1 encephalopathy: in-depth phenotyping and case-by-case analysis. | Kim SY | Orphanet journal of rare diseases | 2020 | PMID: 33298085 |
| Impact of on-site clinical genetics consultations on diagnostic rate in children and young adults with autism spectrum disorder. | Munnich A | Molecular autism | 2019 | PMID: 31406558 |
| Genomic analysis identifies masqueraders of full-term cerebral palsy. | Takezawa Y | Annals of clinical and translational neurology | 2018 | PMID: 29761117 |
| Movement disorder in GNAO1 encephalopathy associated with gain-of-function mutations. | Feng H | Neurology | 2017 | PMID: 28747448 |
| Impact of clinical exomes in neurodevelopmental and neurometabolic disorders. | Evers C | Molecular genetics and metabolism | 2017 | PMID: 28688840 |
| Expanding Phenotype of De Novo Mutations in GNAO1: Four New Cases and Review of Literature. | Schorling DC | Neuropediatrics | 2017 | PMID: 28628939 |
| GNAO1 encephalopathy: Broadening the phenotype and evaluating treatment and outcome. | Danti FR | Neurology. Genetics | 2017 | PMID: 28357411 |
| Clinical Course of Six Children With GNAO1 Mutations Causing a Severe and Distinctive Movement Disorder. | Ananth AL | Pediatric neurology | 2016 | PMID: 27068059 |
| Diagnostic exome sequencing provides a molecular diagnosis for a significant proportion of patients with epilepsy. | Helbig KL | Genetics in medicine : official journal of the American College of Medical Genetics | 2016 | PMID: 26795593 |
| Phenotypic spectrum of GNAO1 variants: epileptic encephalopathy to involuntary movements with severe developmental delay. | Saitsu H | European journal of human genetics : EJHG | 2016 | PMID: 25966631 |
| Enhanced utility of family-centered diagnostic exome sequencing with inheritance model-based analysis: results from 500 unselected families with undiagnosed genetic conditions. | Farwell KD | Genetics in medicine : official journal of the American College of Medical Genetics | 2015 | PMID: 25356970 |
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Text-mined citations for rs797044951 ...
HelpThese citations are identified by LitVar using
the rs number, so they may include citations for more than one variant
at this location. Please review the LitVar results carefully for your
variant of interest.
Record last updated Sep 29, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.