ClinVar Miner

Submissions for variant NM_001110219.3(GJB6):c.458T>C (p.Val153Ala)

gnomAD frequency: 0.00001  dbSNP: rs779119807
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001996923 SCV002224728 uncertain significance Autosomal recessive nonsyndromic hearing loss 1A; Autosomal recessive nonsyndromic hearing loss 1B; Autosomal dominant nonsyndromic hearing loss 3B; Hidrotic ectodermal dysplasia syndrome 2024-03-13 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 153 of the GJB6 protein (p.Val153Ala). This variant is present in population databases (rs779119807, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with GJB6-related conditions. ClinVar contains an entry for this variant (Variation ID: 1447794). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt GJB6 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.

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