Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000036258 | SCV000059910 | likely pathogenic | Rare genetic deafness | 2012-12-11 | criteria provided, single submitter | clinical testing | The Ile232Thr variant in POU3F4 has not been reported in the literature nor prev iously identified by our laboratory. It is also absent from large and broad Euro pean American and African American populations by the NHLBI Exome Sequencing Pro ject (http://evs.gs.washington.edu/EVS). Computational analyses (biochemical ami no acid properties, conservation, AlignGVGD, PolyPhen2, and SIFT) suggest that t he Ile232Thr variant may impact the protein, though this information is not pred ictive enough to determine pathogenicity. This variant is within the highly con served POU specific domain (amino acid 194-260). Except for one common variant ( p.Gly237Ala; dbSNP rs5921979), all other missense variants in this region have o nly been identified in individuals with X-linked hearing loss. Given the locatio n of the variant and the unique phenotypic presentation that is reasonably speci fic for POU3F4 (mixed hearing loss with absent modiolus and dilated, bulbous int ernal auditory canal), we feel this variant is likely pathogenic, though additio nal studies are required to fully establish its clinical significance. |
| Laboratory of Molecular Genetics, |
RCV003445093 | SCV003932337 | likely pathogenic | X-linked mixed hearing loss with perilymphatic gusher | 2023-05-25 | no assertion criteria provided | clinical testing | present in 3 affected male patients in one family |