Description
This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 80 of the GJB1 protein (p.Gln80Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with Charcot-Marie-Tooth disease (PMID: 7580242, 10737979, 17353473; Invitae). ClinVar contains an entry for this variant (Variation ID: 246096). 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 expected to disrupt GJB1 protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change does not substantially affect GJB1 function (PMID: 15006706). This variant disrupts the p.Gln80 amino acid residue in GJB1. Other variant(s) that disrupt this residue have been observed in individuals with GJB1-related conditions (PMID: 22464564, 28286897), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.
# | Sample | Method | Observation |
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Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences |
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1 | germline | unknown | not provided | not provided | not provided | | not provided | not provided | not provided | not provided |