ClinVar Miner

Submissions for variant NM_002074.5(GNB1):c.229G>A (p.Gly77Ser) (rs758432471)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000622797 SCV000742305 likely pathogenic Inborn genetic diseases 2017-04-04 criteria provided, single submitter clinical testing
Invitae RCV001384919 SCV001584609 pathogenic not provided 2018-05-01 criteria provided, single submitter clinical testing 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 small physicochemical difference between glycine and serine. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has been reported to be de novo in individuals affected with GNB1-related neurodevelopmental delay and hypotonia (PMID: 27108799, Invitae). ClinVar contains an entry for this variant (Variation ID: 224713). 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. The p.Gly77 amino acid residue in GNB1 has been determined to be clinically significant (PMID: 27759915). This suggests that variants that disrupt this residue are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.
CeGaT Praxis fuer Humangenetik Tuebingen RCV001384919 SCV001747424 pathogenic not provided 2021-05-01 criteria provided, single submitter clinical testing
GeneDx RCV001384919 SCV001769566 pathogenic not provided 2021-04-15 criteria provided, single submitter clinical testing 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 variant is associated with the following publications: (PMID: 30504930, 29174093, 27759915, 27108799)
Institute for Genomic Medicine, Columbia University,Columbia University Medical Center RCV000210256 SCV000266334 pathogenic Global developmental delay; Muscular hypotonia 2016-02-10 no assertion criteria provided research
University of Washington Center for Mendelian Genomics, University of Washington RCV000755059 SCV000882875 likely pathogenic Seizures; hypotonia; Neurodevelopmental Disability 2016-05-05 no assertion criteria provided research
University of Washington Center for Mendelian Genomics, University of Washington RCV001291375 SCV001479849 likely pathogenic Autism spectrum disorder no assertion criteria provided research

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