ClinVar Miner

Submissions for variant NM_002074.5(GNB1):c.227A>G (p.Asp76Gly)

dbSNP: rs869312821
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001556774 SCV001778412 pathogenic not provided 2021-06-29 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek et al., 2016); 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: 27535533, 27108799)
Invitae RCV001556774 SCV002138600 pathogenic not provided 2022-11-01 criteria provided, single submitter clinical testing This variant disrupts the p.Asp76 amino acid residue in GNB1. Other variant(s) that disrupt this residue have been observed in individuals with GNB1-related conditions (PMID: 27108799), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic. 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 GNB1 protein function. ClinVar contains an entry for this variant (Variation ID: 224711). This missense change has been observed in individual(s) with intellectual disability syndrome (PMID: 27108799). 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 aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 76 of the GNB1 protein (p.Asp76Gly).
Genomics And Bioinformatics Analysis Resource, Columbia University RCV000210265 SCV000266332 pathogenic Global developmental delay; Intellectual disability; Infantile muscular hypotonia; Hypotonia 2016-02-10 no assertion criteria provided research
OMIM RCV000225254 SCV000282057 pathogenic Intellectual disability, autosomal dominant 42 2021-11-02 no assertion criteria provided literature only
OMIM RCV000225357 SCV000282058 pathogenic Acute lymphoid leukemia 2021-11-02 no assertion criteria provided literature only
University of Washington Center for Mendelian Genomics, University of Washington RCV000755052 SCV000882868 likely pathogenic Seizure; Hypotonia; Neurodevelopmental Disability 2016-05-05 no assertion criteria provided research

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