The filtering allele frequency (the lower threshold of the 95% of 49/35,440) of the c.4463A>T (p.Asp1488Val) variant in OTOF is 0.107% for Latino/Admixed American alleles in gnomAD v2, which is a higher frequency than would be expected for an autosomal recessive pathogenic variant based on the thresholds defined by the ClinGen Hearing Loss Expert Panel (BS1_Supporting). The REVEL computational prediction tool produced a score of 0.805, which is above the threshold necessary to apply PP3. While this variant has been observed in at least 6 probands with hearing loss, none of these individuals had a second variant identified in OTOF (Partners Laboratory for Molecular Medicine internal data, ClinVar SCV000065239.6). In summary, the clinical significance of this variant is uncertain. ACMG/AMP criteria applied, as specified by the Hearing Loss Expert Panel: BS1_Supporting, PP3.