ClinVar Miner

Submissions for variant NM_001378609.3(OTOGL):c.4600+1G>T

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
King Laboratory, University of Washington RCV003155568 SCV003844143 likely pathogenic Autosomal recessive nonsyndromic hearing loss 84B 2023-02-28 criteria provided, single submitter research This variant was found in compound heterozygosity with an OTOGL splicing variant in a patient with bilateral sensorineural hearing loss of onset <18 years, in a study of pediatric hearing loss conducted by the King Laboratory (Carlson RJ et al. JAMA-OtoHNS 2023). This patient's family has no other history of hearing loss. This variant is a single base pair substitution that is predicted to alter splicing. At the donor splice of OTOGL exon 39, the sequence change is CTT|gtaagt > CTT|ttaagt, NNSPLICE is 0.98 and 0.00 and MaxEnt is 8.00 and -0.50 for reference and mutant sequences, respectively. Consequences of altered splicing are skipping of exon 39 resulting in a 178bp message deletion and a premature stop at codon 1483 of 2318. As of January 2023, this variant has not been reported to ClinVar and is not found on gnomAD. Based on compound heterozygosity with a loss-of-function variant, the prediction that this variant leads to a truncated protein, and goodness of fit of genotype to phenotype, we conclude that this variant is likely pathogenic.

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