ClinVar Miner

Submissions for variant NM_001292063.2(OTOG):c.5194C>T (p.Gln1732Ter)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV002290905 SCV002578319 uncertain significance not provided 2022-04-06 criteria provided, single submitter clinical testing Nonsense 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
MGZ Medical Genetics Center RCV002290904 SCV002579804 pathogenic Autosomal recessive nonsyndromic hearing loss 18B 2021-12-09 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV002290905 SCV004518664 pathogenic not provided 2023-08-19 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln1744*) in the OTOG gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in OTOG are known to be pathogenic (PMID: 23122587). This variant is present in population databases (no rsID available, gnomAD 0.008%). 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: 1708596). For these reasons, this variant has been classified as Pathogenic.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV004017923 SCV004848849 likely pathogenic Rare genetic deafness 2022-11-03 criteria provided, single submitter clinical testing The p.Gln1744X variant in OTOG has not been reported in individuals with nonsyndromic hearing loss and has been identified in 1/15290 Latino chromosomes by gnomAD (https://gnomad.broadinstitute.org/). This nonsense variant leads to a premature termination codon at position 1744, which is predicted to lead to a truncated or absent protein. Loss of function of the OTOG 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: PM2_supporting, PVS1.

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