ClinVar Miner

Submissions for variant NM_001292063.2(OTOG):c.3457C>T (p.Arg1153Ter)

gnomAD frequency: 0.00004  dbSNP: rs772430523
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Total submissions: 3
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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 RCV000614011 SCV000712281 likely pathogenic Rare genetic deafness 2016-06-27 criteria provided, single submitter clinical testing The p.Arg1165X variant in OTOG has not been reported in individuals with hearing loss. Data from large population studies are insufficient to assess the frequen cy of this variant. This nonsense variant introduces a premature termination cod on at position 1165, which is predicted to lead 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 (Schraders 2012), and disruption of OTOG in m ice resulted in deafness supporting a loss-of-function mechanism for the disease (Simmler 2000). In summary, although additional evidence is required to strengt hen the association between OTOG and hearing loss, available data support that t he p.Arg1165X variant is likely pathogenic.
Fulgent Genetics, Fulgent Genetics RCV002476351 SCV002799966 likely pathogenic Autosomal recessive nonsyndromic hearing loss 18B 2021-07-14 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV002531142 SCV002942344 pathogenic not provided 2022-03-18 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 505150). This variant has not been reported in the literature in individuals affected with OTOG-related conditions. This variant is present in population databases (rs772430523, gnomAD 0.006%). This sequence change creates a premature translational stop signal (p.Arg1165*) 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).

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