Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000156766 | SCV000206487 | likely pathogenic | Rare genetic deafness | 2015-07-30 | criteria provided, single submitter | clinical testing | The p.Arg323His variant in POU3F4 has not been previously reported in individual s with hearing loss or in large population studies. Computational prediction too ls and conservation analyses suggest that the Arg323His variant may impact the p rotein. In addition, two different variants at this position (p.Arg323Gly and p. Arg323Cys) have been identified in the hemizygous state in two different individ uals with hearing loss (de Kok 1997, LMM unpublished data). One of these individ uals had a mixed hearing loss and perilymphatic gusher upon stapedectomy, consis tent with a POU3F4-related hearing loss (de Kok 1997). Furthermore, this variant is located in the POU homeodomain, where most pathogenic missense variants have been identified in this gene (de Kok 1997, Lee 2009). This data suggests that v ariants at the p.Arg323 position are not tolerated. The presence of this variant in three affected family members, two of whom are hemizygous, increases the lik elihood that the p.Arg323His variant is pathogenic. In summary, although additio nal studies are required to fully establish its clinical significance, this vari ant is likely pathogenic. |
| Service de Biologie Medicale, |
RCV001786336 | SCV001712148 | likely pathogenic | X-linked mixed hearing loss with perilymphatic gusher | 2019-09-30 | no assertion criteria provided | clinical testing |