Suzanne de Bruijn

267 Exploring the missing heritability in subjects with hearing loss and EVA Table S4. Compound heterozygous or homozygous variants in arHL-associated genes Case Class Gene Transcript cDNA Protein In-house AF (%) gnomAD AF (%) CADD_ PHRED SIFT PPH2 Mutation Taster SpliceAI ACMG SLC012 M1 OTOGL NM_173591.3 c.890C>T p.(Pro297Leu) 0.09 0.12 22.5 0 1.0 Disease causing - UV2 OTOGL NM_173591.3 c.1369G>T p.(Val457Leu) 0.02 0.00 15.4 0 0.683 Disease causing - UV3 Homozygous or compound heterozygous variants detected in coding or splice site regions (+/14 nucleotides) of genes associated with autosomal recessive hearing loss (arHL). Variants are selected based on an allele frequency of ≤0.5% in gnomAD and the in-house database. Scores that meet the thresholds for pathogenicity as described in the methods section are indicated in red. Thresholds for pathogenicity: CADD-PHRED (≥15), SIFT (≤0.05), PolyPhen-2 (≥0.450), MutationTaster (deleterious) and spliceAI (≥0.1). In-house AF, allele frequency (%) in in-house database (~7,500 exomes); GnomAD AF, allele frequency (%) in gnomAD database V.2.1.1; CADD_PHRED, Combined Annotation Dependent Depletion PHRED score; SIFT, Scale-Invariant Feature Transform; PPH2, Poly-Phen-2 score; MutationTaster (prob), MutationTaster score with probability (0-1); spliceAI, splicing prediction score; ClinVar, ACMG, variant classification according to the American College of Medical Genetics and Genomics (ACMG) classification guidelines 1 ; UV2, likely benign; UV3, uncertain significance.