ClinVar Miner

Submissions for variant NM_001277269.1(OTOG):c.2500C>T (p.Gln834Ter) (rs554847663)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000578779 SCV000680934 likely pathogenic not provided 2017-05-10 criteria provided, single submitter clinical testing The Q834X variant in the OTOG gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The Q834X variant is observed in 6/3270 (0.18%) alleles from individuals of non-Finnish European background in the ExAC data set and has also been identified on 37/62356 individuals undergoing testing at GeneDx, including as an apparently homozygous variant in one presumably healthy individual (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). Based on the information currently available, we interpret Q834X as a likely pathogenic variant.
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000616086 SCV000712161 likely pathogenic Rare genetic deafness 2018-04-11 criteria provided, single submitter clinical testing The p.Gln834X variant in OTOG has been identified by our laboratory in one indiv idual with mild hearing loss who had a second nonsense variant in OTOG, and in t he heterozygous state in two additional individuals with hearing loss, one of wh om carried a variant in another gene which accounted for the hearing loss. It ha s also been identified in 0.09% (53/57364) of European chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs5548476 63). Although this variant has been seen in the general population, its frequenc y is low enough to be consistent with the carrier frequency for recessive hearin g loss. This nonsense variant leads to a premature termination codon at position 834, which is predicted to lead to a truncated or absent protein. In summary, a lthough additional studies are required to fully establish its clinical signific ance, the p.Gln834X variant is likely pathogenic. ACMG/AMP Criteria applied: PVS 1, PM3.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000578779 SCV000891954 likely pathogenic not provided 2019-05-01 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000477813 SCV000893872 likely pathogenic Deafness, autosomal recessive 18b 2018-10-31 criteria provided, single submitter clinical testing
Genomic Medicine Lab, University of California San Francisco RCV001007897 SCV001167603 likely pathogenic Seizures; Intellectual disability 2019-02-07 criteria provided, single submitter clinical testing
Invitae RCV000578779 SCV001206868 pathogenic not provided 2019-12-21 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln834*) in the OTOG gene. It is expected to result in an absent or disrupted protein product. While this variant is present in population databases (rs554847663), the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with OTOG-related conditions. ClinVar contains an entry for this variant (Variation ID: 417941). Loss-of-function variants in OTOG are known to be pathogenic (PMID: 23122587). For these reasons, this variant has been classified as Pathogenic.
Division of Human Genetics,Children's Hospital of Philadelphia RCV000477813 SCV000536895 likely pathogenic Deafness, autosomal recessive 18b 2016-07-19 no assertion criteria provided research

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