Submissions for variant NM_001378609.3(OTOGL):c.5449C>T (p.Arg1817Ter)

gnomAD frequency: 0.00003  dbSNP: rs768620276

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000497321	SCV000589683	pathogenic	not provided	2024-06-05	criteria provided, single submitter	clinical testing	Identified with a second OTOGL variant (phase unknown) in patients with bilateral childhood-onset sensorineural hearing loss referred for genetic testing at GeneDx and in published literature (PMID: 35580552); Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 23352160, 35580552)
CeGaT Center for Human Genetics Tuebingen	RCV000497321	SCV001747658	likely pathogenic	not provided	2021-12-01	criteria provided, single submitter	clinical testing
MGZ Medical Genetics Center	RCV002289684	SCV002580419	pathogenic	Autosomal recessive nonsyndromic hearing loss 84B	2021-12-22	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002289684	SCV002805687	pathogenic	Autosomal recessive nonsyndromic hearing loss 84B	2021-08-25	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000497321	SCV003290828	pathogenic	not provided	2024-02-27	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg1808*) 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). 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 variant has not been reported in the literature in individuals affected with OTOGL-related conditions. ClinVar contains an entry for this variant (Variation ID: 432017). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000497321	SCV001952780	pathogenic	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000497321	SCV001974850	pathogenic	not provided		no assertion criteria provided	clinical testing