Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| ARUP Laboratories, |
RCV000757589 | SCV000885878 | uncertain significance | not provided | 2017-07-31 | criteria provided, single submitter | clinical testing | The p.Gly898Asp variant (rs772312557) has not been reported in the medical literature, nor has it been previously identified in our laboratory. It is listed in the Genome Aggregation Database (gnomAD) browser with an overall frequency of 0.001% (identified in 3 out of 234,434 chromosomes). The glycine at codon 898 is moderately conserved considering 12 species (Alamut software v2.9), and computational analyses return mixed results regarding the effect of this variant on OTOF protein structure/function (SIFT: tolerated, PolyPhen2: possibly damaging, and Mutation Taster: disease causing). Thus, based on the available information, the clinical significance of the p.Gly898Asp variant cannot be determined with certainty. |
| Invitae | RCV000757589 | SCV003486319 | uncertain significance | not provided | 2022-06-27 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 898 of the OTOF protein (p.Gly898Asp). This variant is present in population databases (rs772312557, gnomAD 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: 618773). 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. |
| Ambry Genetics | RCV003353016 | SCV004062454 | uncertain significance | Inborn genetic diseases | 2023-07-19 | criteria provided, single submitter | clinical testing | The c.2693G>A (p.G898D) alteration is located in exon 23 (coding exon 23) of the OTOF gene. This alteration results from a G to A substitution at nucleotide position 2693, causing the glycine (G) at amino acid position 898 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |