Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
King Laboratory, |
RCV003155579 | SCV003844168 | pathogenic | Autosomal recessive nonsyndromic hearing loss 23 | 2023-02-28 | criteria provided, single submitter | research | This variant occurred in homozygosity in an individual 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). At the time of recruitment, this patient did not have any known visual impairment (age 7y). This patient's family has no other history of hearing loss. This variant is a five base pair insertion that leads to a frameshift that is predicted to cause the addition of 198 incorrect amino acids and an abnormally long protein of 1814 rather than 1783 amino acids. Only the PDCH15 isoform critical to hearing, and not the others, would be changed by this variant (PMID: 32747562, 24940003). As of January 2023, this variant has not been reported to ClinVar and is not found on gnomAD. Based on homozgosity, consistently predicted functional effect, and goodness of fit of genotype to phenotype, we conclude that this variant is pathogenic. |