ClinVar Miner

Submissions for variant NM_153212.3(GJB4):c.65G>A (p.Arg22His)

dbSNP: rs80358212
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001836700 SCV002097429 uncertain significance not provided 2022-01-31 criteria provided, single submitter clinical testing 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: 31589614, 12648223)
Labcorp Genetics (formerly Invitae), Labcorp RCV001836700 SCV005766809 uncertain significance not provided 2024-08-14 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 22 of the GJB4 protein (p.Arg22His). This variant is present in population databases (rs80358212, gnomAD 0.01%). This missense change has been observed in individual(s) with erythrokeratodermia variabilis (PMID: 12648223). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 5008). 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 GJB4 protein function with a positive 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.
Department of Pathology and Laboratory Medicine, Sinai Health System RCV000005311 SCV006059300 uncertain significance Erythrokeratodermia variabilis et progressiva 2 2022-08-02 criteria provided, single submitter research
OMIM RCV000005311 SCV000025489 pathogenic Erythrokeratodermia variabilis et progressiva 2 2003-04-01 no assertion criteria provided literature only

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