Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000213910 | SCV000271374 | pathogenic | Rare genetic deafness | 2016-04-07 | criteria provided, single submitter | clinical testing | The p.Pro175fs variant in GJB2 has not been previously reported in individuals w ith hearing loss. This variant was absent from large population studies, though the ability of these studies to accurately detect indels may be limited. This va riant is predicted to cause a frameshift, which alters the protein?s amino acid sequence beginning at position 175 and leads to a premature termination codon 31 amino acids downstream. This alteration is then predicted to lead to a truncate d or unstable protein. In summary, this variant meets the criteria to be classif ied as pathogenic for autosomal recessive hearing loss based on the predicted im pact of the variant. |
Invitae | RCV001382464 | SCV001581238 | pathogenic | not provided | 2022-08-22 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Pro175Glyfs*31) in the GJB2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 52 amino acid(s) of the GJB2 protein. For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the GJB2 protein in which other variant(s) (p.Cys211Leufs*5) have been determined to be pathogenic (PMID: 9529365, 12910486, 20863150). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 228350). This variant has not been reported in the literature in individuals affected with GJB2-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.01%). |