Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Eurofins Ntd Llc |
RCV000732183 | SCV000860103 | uncertain significance | not provided | 2018-03-27 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV001336339 | SCV001529700 | uncertain significance | Autosomal recessive nonsyndromic hearing loss 18B | 2018-08-09 | criteria provided, single submitter | clinical testing | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. |
| Laboratory for Molecular Medicine, |
RCV001449713 | SCV001652969 | uncertain significance | not specified | 2021-02-17 | criteria provided, single submitter | clinical testing | The p.Phe214del variant in OTOG has not been previously reported in individuals with hearing loss but has been identified in 0.18% (125/71330) of European chromosomes by gnomAD (http://gnomad.broadinstitute.org). The variant has been reported in ClinVar (Variation ID 596372). This variant is a an in-frame deletion of one amino acid at position 214 and is not predicted to alter the protein reading frame. Thus, it is unclear if this deletion will impact the protein. In summary, the clinical significance of this variant is uncertain. ACMG/AMP criteria applied: BS1_Supporting. |
| Invitae | RCV000732183 | SCV002160608 | uncertain significance | not provided | 2022-09-27 | criteria provided, single submitter | clinical testing | This variant, c.639_641del, results in the deletion of 1 amino acid(s) of the OTOG protein (p.Phe214del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs753906203, gnomAD 0.2%), and has an allele count higher than expected for a pathogenic variant. 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: 596372). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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. |
| Victorian Clinical Genetics Services, |
RCV001336339 | SCV002768428 | uncertain significance | Autosomal recessive nonsyndromic hearing loss 18B | 2020-10-19 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.1.1, this variant is classified as 3B-VUS. Following criteria are met: 0102 - Loss-of-function is a known mechanism of disease for this gene. (N) 0106 - This gene is known to be associated with autosomal recessive disease. (N) 0216 - In-frame insertion/deletion in a non-repetitive region that has low conservation (exon 6). (P) 0251 - Variant is heterozygous. (N) 0304 - Variant is present in gnomAD (v2) <0.01 for a recessive condition (167 heterozygotes, 0 homozygotes). (P) 0600 - Variant is located in an annotated domain or motif (VWD domain; NCBI, PDB). (N) 0705 - No comparable variants have previous evidence for pathogenicity. (N) 0808 - Previous reports of pathogenicity are inconclusive. The variant has previously been classified as a VUS (ClinVar). (N) 0905 - No segregation evidence has been identified for this variant. (N) 1007 - No published functional evidence has been identified for this variant. (N) 1208 - Inheritance information for this variant is not currently available. (N) Legend: (P) - Pathogenic, (N) - Neutral, (B) - Benign |