Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000151598 | SCV000199763 | uncertain significance | not specified | 2013-05-09 | criteria provided, single submitter | clinical testing | The Arg1448Cys variant in OTOF has not been reported in individuals affected wit h hearing loss or in large population databases. Computational analyses (biochem ical amino acid properties, conservation, AlignGVGD, PolyPhen2, and SIFT) sugges t that the Arg1448Cys variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, additional data i s needed to determine the clinical significance of this variant. |
| Invitae | RCV001850069 | SCV002285171 | uncertain significance | not provided | 2021-09-01 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with cysteine at codon 1448 of the OTOF protein (p.Arg1448Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs727503355, ExAC 0.02%). This variant has not been reported in the literature in individuals affected with OTOF-related conditions. ClinVar contains an entry for this variant (Variation ID: 164845). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |