ClinVar Miner

Submissions for variant NM_004004.6(GJB2):c.560A>G (p.Glu187Gly)

dbSNP: rs1451982228
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001766458 SCV002000173 uncertain significance not provided 2020-11-02 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; Has not been previously published as pathogenic or benign to our knowledge
PreventionGenetics, part of Exact Sciences RCV004527732 SCV004109875 uncertain significance GJB2-related disorder 2022-11-22 criteria provided, single submitter clinical testing The GJB2 c.560A>G variant is predicted to result in the amino acid substitution p.Glu187Gly. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Labcorp Genetics (formerly Invitae), Labcorp RCV001766458 SCV005827669 likely pathogenic not provided 2025-01-18 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 187 of the GJB2 protein (p.Glu187Gly). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of autosomal recessive GJB2-related conditions (internal data). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 560670). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt GJB2 protein function with a positive predictive value of 95%. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Clinical Molecular Genetics Laboratory, Johns Hopkins All Children's Hospital RCV000678890 SCV000805083 uncertain significance Hearing loss 2012-01-04 no assertion criteria provided clinical testing

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