Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV004018168 | SCV004848668 | likely pathogenic | Rare genetic deafness | 2022-06-23 | criteria provided, single submitter | clinical testing | The p.Glu1165ValfsX6 variant in OTOGL has not been previously reported in individuals with nonsyndromic hearing loss, but has been identified in 0.009% (4/41434) of African/African American chromosomes by gnomAD (http://gnomad.broadinstitute.org). However, this frequency is low enough to be consistent with a recessive allele frequency. This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 1165 and leads to a premature termination codon 6 amino acids downstream. Loss of function of the OTOGL gene is an established disease mechanism in autosomal recessive nonsyndromic hearing loss. In summary, although additional studies are required to fully establish its clinical significance, this variant meets criteria to be classified as likely pathogenic for autosomal recessive nonsyndromic hearing loss. ACMG/AMP Criteria applied: PVS1, PM2_Supporting. |
| Gene |
RCV004780703 | SCV005390530 | uncertain significance | not provided | 2024-03-18 | criteria provided, single submitter | clinical testing | Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Has not been previously published as pathogenic or benign to our knowledge |