ClinVar Miner

Submissions for variant NM_001378609.3(OTOGL):c.1585C>T (p.Gln529Ter)

gnomAD frequency: 0.00007  dbSNP: rs371465450
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000598640 SCV000710001 pathogenic not provided 2018-09-17 criteria provided, single submitter clinical testing The Q520X variant in the OTOGL gene has been reported previously in association with hearing impairment in an affected individual who was compound heterozygous for the Q520X variant and another nonsense variant (Bonnet et al., 2013). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The Q520X variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). We interpret Q520X as a pathogenic variant.
Invitae RCV000598640 SCV003441146 pathogenic not provided 2023-04-07 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 503724). This premature translational stop signal has been observed in individual(s) with OTOGL-related conditions (PMID: 23850727). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change creates a premature translational stop signal (p.Gln520*) in the OTOGL gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in OTOGL are known to be pathogenic (PMID: 23122586). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. For these reasons, this variant has been classified as Pathogenic.
CeGaT Center for Human Genetics Tuebingen RCV000598640 SCV004700115 pathogenic not provided 2024-02-01 criteria provided, single submitter clinical testing OTOGL: PVS1, PM2
GenomeConnect, ClinGen RCV000844972 SCV000986798 not provided Autosomal recessive nonsyndromic hearing loss 84B no assertion provided phenotyping only Variant interpreted as Pathogenic and reported most recently on 06-29-2018 by GTR ID 26957. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant.

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