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

gnomAD frequency: 0.00001  dbSNP: rs758432471

Total submissions: 9

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	2022-01-27	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Gly77 amino acid residue in GNB1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 27759915). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. ClinVar contains an entry for this variant (Variation ID: 224713). This missense change has been observed in individual(s) with GNB1-related neurodevelopmental delay and hypotonia (PMID: 27108799; Invitae). 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 glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 77 of the GNB1 protein (p.Gly77Ser).
CeGaT Center for Human Genetics Tuebingen	RCV001384919	SCV001747424	pathogenic	not provided	2021-05-01	criteria provided, single submitter	clinical testing
GeneDx	RCV001384919	SCV001769566	pathogenic	not provided	2022-01-07	criteria provided, single submitter	clinical testing	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: 27108799, 27759915, 29174093, 30504930)
MGZ Medical Genetics Center	RCV002288841	SCV002580998	likely pathogenic	Intellectual disability, autosomal dominant 42	2022-07-01	criteria provided, single submitter	clinical testing
Institute Of Human Genetics Munich, Klinikum Rechts Der Isar, Tu München	RCV002288841	SCV004045955	pathogenic	Intellectual disability, autosomal dominant 42	2023-05-23	criteria provided, single submitter	clinical testing
Genomics And Bioinformatics Analysis Resource, Columbia University	RCV001842964	SCV000266334	pathogenic	Global developmental delay; Hypotonia	2016-02-10	no assertion criteria provided	research
University of Washington Center for Mendelian Genomics, University of Washington	RCV000755059	SCV000882875	likely pathogenic	Seizure; 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