Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV003732237 | SCV004538118 | likely pathogenic | not provided | 2024-01-25 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 34 of the OTOGL gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in OTOGL are known to be pathogenic (PMID: 23122586). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with OTOGL-related conditions. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
Center for Genomic Medicine, |
RCV003989861 | SCV004806068 | uncertain significance | Autosomal recessive nonsyndromic hearing loss 84B | 2024-03-25 | criteria provided, single submitter | clinical testing | |
Laboratory for Molecular Medicine, |
RCV004018006 | SCV004848709 | likely pathogenic | Rare genetic deafness | 2022-06-30 | criteria provided, single submitter | clinical testing | The c.4172+1G>A variant in OTOGL has not been previously reported in individuals with nonsyndromic hearing loss and was absent from large population studies. This variant occurs within the canonical splice site (+/- 1,2) and is predicted to cause altered splicing leading to an abnormal or absent protein. Loss of function of the OTOGL gene is an established disease mechanism in autosomal recessive nonsyndromic 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_Supporting. |