Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000612387 | SCV000711175 | uncertain significance | not specified | 2016-10-06 | criteria provided, single submitter | clinical testing | The p.Arg1448His variant in OTOF has not been previously reported in individuals with hearing loss. It has been identified in 1/66162 European chromosomes by th e Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs37 3858563). Although this variant has been seen in the general population, its fre quency is not high enough to rule out a pathogenic role. Computational predictio n tools and conservation analyses suggest that this variant may impact the prote in, though this information is not predictive enough to determine pathogenicity. In summary, the clinical significance of the p.Arg1448His variant is uncertain. |
| Invitae | RCV001868010 | SCV002193108 | uncertain significance | not provided | 2021-08-14 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with histidine at codon 1448 of the OTOF protein (p.Arg1448His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs373858563, ExAC 0.002%). 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: 504658). 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. |