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NM_002074.5(GNB1):c.229G>A (p.Gly77Ser)

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Interpretation:
Pathogenic/Likely pathogenic​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
7 (Most recent: Aug 5, 2021)
Last evaluated:
May 1, 2021
Accession:
VCV000224713.7
Variation ID:
224713
Description:
single nucleotide variant
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NM_002074.5(GNB1):c.229G>A (p.Gly77Ser)

Allele ID
226500
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
1p36.33
Genomic location
1: 1806513 (GRCh38) GRCh38 UCSC
1: 1737952 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
P62873:p.Gly77Ser
NC_000001.10:g.1737952C>T
NC_000001.11:g.1806513C>T
... more HGVS
Protein change
G77S
Other names
-
Canonical SPDI
NC_000001.11:1806512:C:T
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
Exome Aggregation Consortium (ExAC) 0.00001
Links
ClinGen: CA351379
UniProtKB: P62873#VAR_076645
dbSNP: rs758432471
Varsome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Pathogenic 3 criteria provided, multiple submitters, no conflicts May 1, 2021 RCV001384919.4
Likely pathogenic 1 criteria provided, single submitter Apr 4, 2017 RCV000622797.1
Pathogenic 1 no assertion criteria provided Feb 10, 2016 RCV000210256.1
Neurodevelopmental Disability
hypotonia
Likely pathogenic 1 no assertion criteria provided May 5, 2016 RCV000755059.1
Likely pathogenic 1 no assertion criteria provided - RCV001291375.1

Clinical features observed in individuals with this variant

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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
GNB1 Little evidence for dosage pathogenicity No evidence available GRCh38
GRCh37
61 205

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Likely pathogenic
(Apr 04, 2017)
criteria provided, single submitter
Method: clinical testing
Inborn genetic diseases
Allele origin: germline
Ambry Genetics
Accession: SCV000742305.2
Submitted: (Oct 09, 2020)
Evidence details
Publications
PubMed (1)
Pathogenic
(May 01, 2018)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
Invitae
Accession: SCV001584609.1
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (2)
Comment:
This sequence change replaces glycine with serine at codon 77 of the GNB1 protein (p.Gly77Ser). The glycine residue is highly conserved and there is a … (more)
Pathogenic
(May 01, 2021)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
CeGaT Praxis fuer Humangenetik Tuebingen
Accession: SCV001747424.1
Submitted: (Jul 04, 2021)
Evidence details
Pathogenic
(Apr 15, 2021)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV001769566.1
Submitted: (Aug 05, 2021)
Evidence details
Comment:
Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This … (more)
Pathogenic
(Feb 10, 2016)
no assertion criteria provided
Method: research
Global developmental delay
Muscular hypotonia
Allele origin: de novo
Institute for Genomic Medicine, Columbia University,Columbia University Medical Center
Accession: SCV000266334.1
Submitted: (Mar 13, 2016)
Evidence details
Publications
PubMed (1)
Likely pathogenic
(May 05, 2016)
no assertion criteria provided
Method: research
Neurodevelopmental Disability

Hypotonia

Seizures
Allele origin: unknown
University of Washington Center for Mendelian Genomics, University of Washington
Accession: SCV000882875.1
Submitted: (May 22, 2018)
Evidence details
Likely pathogenic
(-)
no assertion criteria provided
Method: research
Autism spectrum disorder
Allele origin: de novo
University of Washington Center for Mendelian Genomics, University of Washington
Accession: SCV001479849.1
Submitted: (Nov 16, 2020)
Evidence details

Functional evidence

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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.

Citations for this variant

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Title Author Journal Year Link
Genome sequencing identifies multiple deleterious variants in autism patients with more severe phenotypes. Guo H Genetics in medicine : official journal of the American College of Medical Genetics 2019 PMID: 30504930
Acute lymphoblastic leukemia in a child with a de novo germline gnb1 mutation. Brett M American journal of medical genetics. Part A 2017 PMID: 27759915
Germline De Novo Mutations in GNB1 Cause Severe Neurodevelopmental Disability, Hypotonia, and Seizures. Petrovski S American journal of human genetics 2016 PMID: 27108799
Molecular basis for interactions of G protein betagamma subunits with effectors. Ford CE Science (New York, N.Y.) 1998 PMID: 9596582

Text-mined citations for rs758432471...

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These 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 Oct 02, 2021