Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Eurofins Ntd Llc |
RCV000627358 | SCV000703791 | pathogenic | not provided | 2016-12-08 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV000627358 | SCV000748351 | pathogenic | not provided | 2022-05-11 | criteria provided, single submitter | clinical testing | Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Reported by 2 other laboratories in ClinVar as pathogenic, observed in at least one individual with hearing loss and a second nonsense variant in OTOGL (phase unknown); Has not been previously published as pathogenic or benign to our knowledge |
| Laboratory for Molecular Medicine, |
RCV000825570 | SCV000966902 | pathogenic | Rare genetic deafness | 2018-03-01 | criteria provided, single submitter | clinical testing | The p.Trp638X variant in OTOGL has been identified by our laboratory in 1 indivi dual with hearing loss and a second nonsense variant in OTOGL (orientation not t ested yet). It has also been identified in 8/34256 Latino chromosomes by the Gen ome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org/; dbSNP rs377 708973). Although this variant has been seen in the general population, its freq uency is low enough to be consistent with a recessive carrier frequency. This no nsense variant leads to a premature termination codon at position 638, which is predicted to lead to a truncated or absent protein. Loss of function of the OTOG L gene is an established disease mechanism in autosomal recessive hearing loss. In summary, this variant meets our criteria to be classified as pathogenic for h earing loss in an autosomal recessive manner. ACMG/AMP Criteria applied: PVS1; P M2_Supporting; PM3_Supporting. |
| Labcorp Genetics |
RCV000627358 | SCV002228289 | pathogenic | not provided | 2023-11-26 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Trp638*) in the OTOGL gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in OTOGL are known to be pathogenic (PMID: 23122586). This variant is present in population databases (rs377708973, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with OTOGL-related conditions. ClinVar contains an entry for this variant (Variation ID: 498660). For these reasons, this variant has been classified as Pathogenic. |
| Laboratorio de Genetica e Diagnostico Molecular, |
RCV002252175 | SCV002523974 | likely pathogenic | See cases | 2021-04-13 | criteria provided, single submitter | clinical testing | ACMG classification criteria: PVS1, PM2 |