Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000041202 | SCV000064893 | likely pathogenic | Rare genetic deafness | 2019-05-30 | criteria provided, single submitter | clinical testing | The p.Arg833X variant in LOXHD1 been identified in 1 individual with sensorineural hearing loss; however, a second pathogenic variant in this gene was not identified (LMM data). It has also been identified in 0.05% (3/60924) of European chromosomes by gnomAD (https://gnomad.broadinstitute.org). This nonsense variant leads to a premature termination codon at position 833, which is predicted to lead to a truncated or absent protein. Loss of function of the LOXHD1 gene is strongly associated wish autosomal recessive hearing loss. In summary, although additional studies are required to fully establish its clinical significance, this variant meets criteria to be classified as likely pathogenic for autosomal recessive nonsyndromic hearing loss. ACMG/AMP Criteria applied: PVS1, PM2. |
| Ce |
RCV000512767 | SCV000608858 | likely pathogenic | not provided | 2017-03-31 | criteria provided, single submitter | clinical testing | |
| Illumina Laboratory Services, |
RCV000778910 | SCV000915318 | likely pathogenic | Autosomal recessive nonsyndromic hearing loss 77 | 2024-07-22 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000512767 | SCV001218657 | pathogenic | not provided | 2024-01-04 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg833*) in the LOXHD1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in LOXHD1 are known to be pathogenic (PMID: 19732867, 21465660, 25792669). This variant is present in population databases (rs188119157, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with LOXHD1-related conditions. ClinVar contains an entry for this variant (Variation ID: 47930). For these reasons, this variant has been classified as Pathogenic. |
| Department of Otolaryngology – Head & Neck Surgery, |
RCV001375153 | SCV001572111 | likely pathogenic | Hearing impairment | 2021-04-12 | criteria provided, single submitter | clinical testing | PVS1_Strong, PM2_Moderate |
| DASA | RCV000778910 | SCV002588781 | pathogenic | Autosomal recessive nonsyndromic hearing loss 77 | 2022-11-03 | criteria provided, single submitter | clinical testing | The c.2497C>T;p.(Arg833*) variant creates a premature translational stop signal in the LOXHD1 gene. It is expected to result in an absent or disrupted protein product - PVS1. ClinVar contains an entry for this variant (ClinVar ID: 47930) - PS4_supporting. The variant is present at low allele frequencies population databases (rs188119157 – gnomAD 0.0002529%; ABraOM no frequency - https://abraom.ib.usp.br/) - PM2_supporting. In summary, the currently available evidence indicates that the variant is pathogenic. |