ClinVar Miner

Submissions for variant NM_024009.3(GJB3):c.373G>A (p.Gly125Arg)

gnomAD frequency: 0.00004  dbSNP: rs753289516
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001761054 SCV001999867 uncertain significance not provided 2024-08-02 criteria provided, single submitter clinical testing 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
Labcorp Genetics (formerly Invitae), Labcorp RCV001761054 SCV004623508 uncertain significance not provided 2024-09-05 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 125 of the GJB3 protein (p.Gly125Arg). This variant is present in population databases (rs753289516, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with GJB3-related conditions. ClinVar contains an entry for this variant (Variation ID: 1310884). 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 not expected to disrupt GJB3 protein function with a negative predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV004040217 SCV004876992 uncertain significance Inborn genetic diseases 2024-01-03 criteria provided, single submitter clinical testing The c.373G>A (p.G125R) alteration is located in exon 2 (coding exon 1) of the GJB3 gene. This alteration results from a G to A substitution at nucleotide position 373, causing the glycine (G) at amino acid position 125 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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