ClinVar Miner

Submissions for variant NM_001277269.1(OTOG):c.6591G>A (p.Trp2197Ter) (rs1193023501)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000608772 SCV000731645 likely pathogenic Rare genetic deafness 2017-05-16 criteria provided, single submitter clinical testing The p.Trp2197X variant in OTOG has not been previously reported in individuals w ith hearing loss, but has been identified in 1/51754 European chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org/). Althou gh this variant has been seen in the general population, its frequency is low en ough to be consistent with a recessive carrier frequency. This nonsense variant leads to a premature termination codon at position 2197, which is predicted to l ead to a truncated or absent protein. Two loss of function variants in the OTOG gene have been reported to segregate with hearing loss in two families (Schrader s 2012), and disruption of OTOG in mice resulted in deafness supporting a loss-o f-function mechanism for the disease (Simmler 2000). In summary, although additi onal evidence is required to strengthen the gene-disease association for OTOG an d hearing loss, the current data support that the p.Trp2197X variant is likely p athogenic.

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