The variant c.6614C>T (NM_022124.6(CDH23):c.6614C>T (p.Pro2205Leu)) in CDH23 is a missense variant predicted to cause substitution of proline by leucine at amino acid 2205 (p.Pro2205Leu). The highest population minor allele frequency in gnomAD v4.0.0 is 0.000002920 (8/1179896 alleles) in the European (non-Finnish) population, which is lower than the ClinGen Hearing Loss VCEP threshold (<0.00007) for PM2_Supporting, meeting this criterion (PM2_Supporting). The computational predictor REVEL gives a score of 0.342, which is neither above nor below the thresholds predicting a damaging or benign impact on CDH23 function. This variant has been detected in at least 8 individuals with autosomal recessive hearing loss. All of these individuals were homozygous for the variant (1.0 pts; PMIDs: 28501645, 32747562 & LMM Internal Data (SCV000062934.5); PM3). There was a common haplotype found between five affected individuals from three families, one of which had three affected siblings, including a set of twins. Personal communication confirmed the three siblings were sequenced; however, it was not apparent whether the twins were dizygotic or monozygotic and therefore only one twin was counted toward segregation (PP1_Supporting; 28501645). In summary, this variant meets the criteria to be classified as uncertain significance for autosomal recessive Usher syndrome, based on the ACMG/AMP criteria applied, as specified by the ClinGen Hearing Loss VCEP (PM2_Supporting, PM3, PP1_Supporting; Version 2; 11/15/23).