Suzanne de Bruijn

125 A RIPOR2 deletion is a frequent cause of adult-onset hearing loss Table S2. Rare variants in the index cases in genes known to be associated with adHL Family Genome Gene Transcript cDNA Protein In-house AF (%) gnomAD_E AF (%) gnomAD_G AF (%) CADD_ PHRED SIFT PPH2 MutationTaster (prob) ClinVar W18-0470 Chr22: 36681327T>C MYH9 NM_002473.4 c.5323A>G p.(Lys1775Glu) 0.18 0.15 0.19 22.2 0.03 0.120 Disease causing (1.0) UV2 W18-0473 Chr4: 6303119C>T WFS1 NM_006005.3 c.1597C>T p.(Pro533Ser) 0.22 0.07 0.08 19.64 0.00 1.000 Disease causing (1.0) UV1-UV3 Chr22: 36700183G>A MYH9 NM_002473.4 c.2248G>A p.(Asp750Asn) 0.01 0.00 - 20.80 0.00 0.997 Disease causing (1.0) NA W18-1160 Chr11: 76873225A>G MYO7A NM_000260.3 c.1403A>G p.(His468Arg) 0.10 0.01 0.02 19.61 0.01 0.993 Disease causing (1.0) UV3 For none of the variants is an effect on transcript splicing predicted. 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) and MutationTaster (deleterious). Genome, Genomic positions according to GRCh37/hg19; In-house AF, allele frequency (%) in in-house database (~7,500 exomes); GnomAD_E AF and GnomAD_G AF, allele frequencies (%) in respectively gnomAD exome or genome databases; 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); ClinVar, American College of Medical Genetics and Genomics (ACMG) classification of variants as in ClinVar; UV1, benign; UV2, likely benign; UV3, variant with unknown significance; NA, not available.