ClinVar Miner

Submissions for variant NM_001292063.2(OTOG):c.4657G>T (p.Gly1553Ter)

gnomAD frequency: 0.00001  dbSNP: rs897822685
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000600685 SCV000731383 likely pathogenic Rare genetic deafness 2017-01-24 criteria provided, single submitter clinical testing The p.Gly1565X variant in OTOG has not been previously reported in individuals w ith hearing loss or in large population databases. This nonsense variant leads t o a premature termination codon at position 1565, which is predicted to lead to a truncated or absent protein. Two loss of function variants in the OTOG gene ha ve been reported to segregate with hearing loss in two families (Schraders 2012) . Furthermore, disruption of Otog in mice results in deafness, supporting a loss -of-function mechanism for the disease (Simmler 2000). In summary, while the p.G ly1565X variant is likely pathogenic for autosomal recessive nonsyndromic hearin g loss based on the predicted impact of the variant, additional evidence support ing the role of OTOG in hearing loss is needed to definitively establish the cli nical significance of this variant.
GeneDx RCV000760670 SCV000890562 pathogenic not provided 2024-04-01 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; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 36515421)

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