Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001040588 | SCV001204171 | pathogenic | not provided | 2023-08-22 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Cys202*) in the GJB2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 25 amino acid(s) of the GJB2 protein. This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with autosomal recessive nonsyndromic deafness (PMID: 23141775). ClinVar contains an entry for this variant (Variation ID: 627447). This variant disrupts a region of the GJB2 protein in which other variant(s) (p.Leu213*, p.Cys211*) have been determined to be pathogenic (PMID: 15150777, 23141775). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |
| 3billion | RCV001809798 | SCV002059140 | likely pathogenic | Autosomal dominant nonsyndromic hearing loss 3A | 2022-01-03 | criteria provided, single submitter | clinical testing | Stop-gained (nonsense): predicted to result in a loss or disruption of normal protein function through protein truncation. Multiple pathogenic variants are reported in the predicted truncated region (PVS1_S). The variant has been reported to be in trans with a pathogenic variant as either compound heterozygous or homozygous in at least one similarly affected unrelated individual (PMID: 23141775, PM3_M). It is not observed in the gnomAD v2.1.1 dataset (PM2_M). The variant has been reported to co-segregate with the disease in at least one similarly affected relative/individual in the same family or similarly affected unrelated family (PMID: 23141775, PP1_P).Therefore, this variant is classified as likely pathogenic according to the recommendation of ACMG/AMP guideline. |
| Genetic Testing Center for Deafness, |
RCV000770823 | SCV000902321 | pathogenic | Autosomal recessive nonsyndromic hearing loss 1A | 2019-02-26 | no assertion criteria provided | case-control |