Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000645728 | SCV000767481 | uncertain significance | Autosomal recessive nonsyndromic hearing loss 1A; Autosomal recessive nonsyndromic hearing loss 1B; Autosomal dominant nonsyndromic hearing loss 3B; Hidrotic ectodermal dysplasia syndrome | 2023-03-04 | criteria provided, single submitter | clinical testing | 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. 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. ClinVar contains an entry for this variant (Variation ID: 536989). This missense change has been observed in individual(s) with hearing loss and a variant in GJB2 (PMID: 17666888). This variant is present in population databases (rs141752846, gnomAD 0.03%). This sequence change replaces cysteine, which is neutral and slightly polar, with glycine, which is neutral and non-polar, at codon 211 of the GJB6 protein (p.Cys211Gly). |
| Gene |
RCV002221570 | SCV002498929 | uncertain significance | not provided | 2022-03-18 | criteria provided, single submitter | clinical testing | Observed heterozygous in a patient with hearing loss in published literature who was also heterozygous for the GJB2 V37A variant (Putcha et al., 2007); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 17666888) |