Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000615378 | SCV000713010 | likely pathogenic | Rare genetic deafness | 2017-06-20 | criteria provided, single submitter | clinical testing | The p.Trp142Arg variant in SOX10 has been reported in one individual with Kallma nn syndrome who had prelingual hearing loss and temporal bone abnormalities, inc luding hypoplasia of the semicircular canals and an enlarged vestibular aqueduct (Pingault 2013). It has also been reported by our laboratory to have likely occ urred de novo in 1 individual with congenital hearing loss and enlarged vestibul ar aqueducts, though parental identity has not been confirmed. This variant has not been identified in large population studies. In vitro studies showed that th e p.Trp142Arg variant altered the ability of SOX10 to localize to the nucleus an d to transactivate MITF and MPZ genes (Pingault 2013). Computational prediction tools and conservation analyses suggest that this variant may impact the protein . In summary, although additional studies are required to fully establish its c linical significance, this variant is likely pathogenic for autosomal dominant h earing loss with temporal bone abnormalities based on its presence in multiple a ffected individuals, likely de novo occurrence, extremely low frequency in the g eneral population, and supportive functional evidence. |
| Genetic Testing Center for Deafness, |
RCV001290172 | SCV001478229 | pathogenic | Waardenburg syndrome type 2E | 2019-01-01 | criteria provided, single submitter | clinical testing |