Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000221473 | SCV000272267 | uncertain significance | not specified | 2016-03-22 | criteria provided, single submitter | clinical testing | Variant classified as Uncertain Significance - Favor Benign. The p.Ala2685Asp va riant in OTOG has been previously reported by our laboratory in one individual w ith hearing loss, in whom a variant affecting the remaining copy of the gene was not identified. Although the coding change identified in this individual (c.805 4_8055delinsAT) was not reported in large population databases, the two componen t variants, c.8054C>A and c.8055C>T were reported in 1/4874 and 1/4880 European chromosomes, respectively, by the Exome Aggregation Consortium (ExAC, http://exa c.broadinstitute.org; dbSNP rs563948391 and rs531303093). While these variants a re likely to represent the c.8054_8055delinsAT variant, at this time we cannot c onfirm that the two variants were identified on the same chromosome in the ExAC cohort. Furthermore, alanine (Ala) at position 2685 is conserved in mammals but not in evolutionarily distant species, with >15 species of birds carry an aspart ic acid (Asp) at this position, raising the possibility that this change may be tolerated. Additional computational prediction tools do not provide strong evide nce for or against an impact to the protein. In summary, while the clinical sign ificance of the p.Ala2685Asp variant is uncertain, the conservation data suggest s that it is more likely to be benign. |
| Gene |
RCV000767213 | SCV000710181 | uncertain significance | not provided | 2023-06-20 | criteria provided, single submitter | clinical testing | In silico analysis supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
| Invitae | RCV000767213 | SCV002197182 | uncertain significance | not provided | 2023-10-13 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 2685 of the OTOG protein (p.Ala2685Asp). This variant is present in population databases (no rsID available, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with OTOG-related conditions. ClinVar contains an entry for this variant (Variation ID: 229106). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests 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. |
| Mayo Clinic Laboratories, |
RCV000767213 | SCV004225379 | uncertain significance | not provided | 2022-02-01 | criteria provided, single submitter | clinical testing | BP4 |