ClinVar Miner

Submissions for variant NM_001292063.2(OTOG):c.7481-5_7482dup (rs1295062471)

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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, Partners HealthCare Personalized Medicine RCV000221901 SCV000272264 uncertain significance not specified 2015-11-10 criteria provided, single submitter clinical testing The c.7517-5_7518dup variant in OTOG has been previously reported in one individ ual with hearing loss; however, a variant affecting the remaining copy of OTOG w as not detected in this individual and an alternate genetic explanation for thei r disease was identified(LMM unpublished data). Data from large population studi es is insufficient to assess the frequency of this variant. This variant is a ta ndem duplication of 7 base pairs that encompass the 3' splice junction of intron 43 in the OTOG gene. However, it is not clear whether this will result in splic ing to occur at a novel 3' splice site downstream of the nascent splice site, wh ich would not impact the protein, or if splicing occurs at the nascent splice si te, which would result in a frameshift of the coding sequence and therefore, be deleterious to the protein. Computational tools predict that splicing would occu r at the novel 3' splice site and thus would not result in a frameshift of the c oding sequence; however, functional studies are needed to determine which of the se scenarios is correct. In summary, the clinical significance of the c.7517-5_7 518dup variant is uncertain.
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000593594 SCV000700763 uncertain significance not provided 2017-05-05 criteria provided, single submitter clinical testing
King Laboratory,University of Washington RCV001507310 SCV001712077 likely pathogenic Deafness, autosomal recessive 18b 2021-03-18 criteria provided, single submitter research OTOG c.7517-5_7518dup is predicted to introduce a cryptic splice acceptor within the sequence of the in-tandem duplication in OTOG intron 43. The cryptic splice acceptor in OTOG intron 43 occurs upstream of the OTOG exon 44 canonical splice and is predicted to result in inclusion of the mutant exon with the 7bp duplication leading to a premature stop. Consequence of this in-tandem duplication would be splicing of OTOG exon 44 occurring at the cryptic splice acceptor and resulting in a 7bp insertion in the OTOG message and premature stop at codon 2510 of 2926.

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