Table 1.
Pathogenic/likely pathogenic variants in Filipino cochlear implantees identified in this study†
| ID | Geno- type |
Gene | Expected MOI |
RefSeq NM_ |
cDNA Variant |
Amino Acid Variant |
Damaging Prediction |
CADD | gnomAD MAF Overall |
gnomAD MAF NFE |
gnomAD MAF EAS |
|---|---|---|---|---|---|---|---|---|---|---|---|
| 2‡ | Het | DFNA5 | DFNA5 | 004403 | c.1277_1279delATG | p.(Asp426del) | MT | -- | 0.0006 | 0 | 0.0005 |
| 4§ | Het | EYA4 | DFNA10 | 004100 | c.1109G>A | p.(Arg370His) | Fa,LRT,mLR, mSVM,MA,MT, PP2_HD/HV, PR,SI |
35 | 0.00004 | 0.00006 | 0 |
| 10‡ | Het | KCNQ4 | DFNA2A | 004700 | c.546C>G | p.(Phe182Leu) | MT | 22 | 0.0003 | 0 | 0.004 |
| 14¶ | Hom | OTOA | DFNB22 | 144672 | c.2301+1G>T | NA | MT | 27.1 | 0 | 0 | 0 |
| 15‡ | Cpd het | CDH23 | DFNB12; AR USH1D |
022124 | c.68–3C>T | NA | MT | -- | 0.0005 | 0.000008 | 0.008 |
| 15‡ | Cpd het | CDH23 | DFNB12; AR USH1D |
022124 | c.4762C>T | p.(Arg1588Trp) | LRT,MA,MT, PP2_HD/HV, PR,SI | 23.3 | 0.0002 | 0.00007 | 0.001 |
| 16 | Het | WFS1 | DFNA6/14/38; AD/AR Wolfram | 006005 | c.708C>G | p.(Ser236Arg) | Fa,LRT,mLR,MT | 12.9 | 0 | 0 | 0 |
| 17‡ | Hom | MYO15A | DFNB3 | 016239 | c.263C>T | p.(Thr88Met) | Fa, PP2_HD | 18.6 | 0.00007 | 0 | 0 |
| 21 | Het | COL4A3 | AD/AR Alport | 000091 |
c.764C >T |
p.(Thr2 55Met) |
Fa,mLR,mSVM, MT,PP2_HD/HV,SI | 33 | 0.00009 | 0.000009 | 0.00006 |
| 26 | Het | MYH14 | DFNA4A; AD PNMHH |
001145809 |
c.2971G >A |
p.(Glu991Lys) | Fa,mLR,mSVM,MA,MT,PP2_HD/HV,PR,SI | 28.9 | 0.00001 | 0 | 0.00007 |
| 28 | Het | CHD7 | AD CHARGE | 017780 |
c.731 2C> G |
p.(Gln24 38Glu) |
LRT,MT, PP2_HD/HV |
25.3 | 0 | 0 | 0 |
All variants listed were not found in Filipino controls from SDFIL and CLHNS. Novel variants are in bold font.
Confirmed to have nonsyndromic hearing impairment (if including GJB2-/SLC26A4-positive patients, total 9 of 15 or 60% of those with genetic variants).
Prior to surgery, patient #4 had a steeply sloping audiogram with 45–50 dB hearing at 500–1000 kHz and profound loss at 4000 Hz. All other patients listed in Table 1 had flat audiograms with severe-to-profound hearing loss. Additional clinical information on these patients were previously provided in reference #3.
Patient #14 has global developmental delay and a history of maternal rubella, low birth weight, exchange transfusion for jaundice, antibiotic treatment and mechanical ventilation for neonatal pneumonia, and intraventricular hemorrhage.
Abbreviations: AD, autosomal dominant; AR, autosomal recessive; CADD, Combined Annotation-Dependent Depletion; Cpd het, compound heterozygous; DFNA#, nonsyndromic autosomal dominant hearing loss; DFNB#, nonsyndromic autosomal recessive hearing loss; EAS, East Asian; Fa, FATHMM; gnomAD, Genome Aggregation Database; HD, HumDiv; Het, heterozygous; Hom, homozygous; HV, HumVar; LRT, Likelihood Ratio Test; MA, MutationAssessor; MAF, minor allele frequency; mLR, MetaLR; MT, MutationTaster; mSVM, MetaSVM; NFE, non-Finnish European; PNMHH, peripheral neuropathy, myopathy, hoarseness and hearing loss; PP2, PolyPhen2; PR, PROVEAN; RefSeq, Reference Sequence; SI, SIFT; USH1D, Usher syndrome Type I