Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000080367 | SCV000112263 | uncertain significance | not provided | 2013-09-05 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000080367 | SCV002259708 | likely pathogenic | not provided | 2023-10-22 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 63 of the GJB2 protein (p.Val63Met). This variant is present in population databases (rs370696868, gnomAD 0.004%). This missense change has been observed in individual(s) with deafness (PMID: 14985372, 17666888, 21366436, 26252218). ClinVar contains an entry for this variant (Variation ID: 94391). 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 GJB2 protein function. This variant disrupts the p.Val63 amino acid residue in GJB2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 17041943; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. |