Table 1.
Details of twelve deaf subjects having causative pathogenic variants or variants of uncertain significance after massive parallel sequencing targeting the genes related with hearing loss.
| Gene (GeneBank No.) | Family ID | Variant | Classification of variants | State | Depth (DP/AD) | Q call (Qual/MQ) | Prediction Algorithm | Conservation Score | MAF | Published reference (PMID) | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Mutation Taster | PolyPhen-2 | SIFT | PhyloP | GERP + + | ExAC, 1000 G | GnomAD* | ||||||||
| Causative (likely) pathogenic variants | ||||||||||||||
| MYO15A (NM_016239) | HL-92 | c.7396-1 G > A | LPa | Het | 61 | 60 | DC | NA | NA | 4.783 | 4.01 | A = 0.00002/1 (ExAC) | A = 0.0001 (2/14966) | This study |
| HL-92 | c.8552 C > T:p.Ala2851Val | Pa | Het | 80 | 60 | DC | PrD | D | 5.319 | 4.41 | T = 0.000008/1 (ExAC) | T = 0.000065, (1/15292) | This study | |
| HL-105 | c.7396-1 G > A | LPa | Het | 85 | 60 | DC | NA | NA | 4.783 | 4.01 | A = 0.00002/1 (ExAC) | A = 0.0001 (2/14966) | This study | |
| HL-105 | c.8324 G > A:p.Arg2775His | Pa | Het | 123 | 60 | DC | PrD | D | 5.89 | 5.1 | T = 0.000008/1 (ExAC) | T = 0.000 (0/245848) | 23767834, This study | |
| MYO7A (NM_000260) | HL-110 | c.1117 C > T:p.Arg373Cys | Pa | Het | 125 | 60 | DC | PrD | D | 4.201 | 5.11 | ND | ND | 22903915, This study |
| HL-110 | c.2239_2240delAG: p.Arg747fs*16 | Pa | Het | 65 | 60 | NA | NA | NA | 1.305_ 3.153 | 2.7 | ND | Del = 0.00002 (1/33480) | 22898263, This study | |
| HL-49 | c.73 G > A:p.Gly25Arg | Pa | Het | 392 | 60 | DC | PrD | D | 5.733 | 4.69 | A = 0.00002/2 (ExAC) | A = 0.000018 (2/110120) | 9002678, This study | |
| HL-49 | c.5233 T > G:p.Trp1745Arg | US | Het | 104 | 60 | DC | PrD | D | 1.028 | 5.13 | ND | ND | This study | |
| Variants of uncertain significance | ||||||||||||||
| MYO15A (NM_016239) | HL-108 | c.8300 A > G:p.Asp2767Gly | US | Het | 53 | 60 | DC | PrD | D | 4.864 | 5.1 | ND | ND | This study |
| HL-108 | c.5603 G > A:p.Arg1868His | US | Het | 62 | 60 | DC | PrD | T | 3.273 | 4.8 | A = 0.0001/15 (ExAC) A = 0.0004/2 (1000 G) | A = 0.0005 (11/18868) | This study | |
| HL-79 | c.442 G > A:p.Glu148Lys | US | Het | 195 | 60 | P | B | T | 1.087 | 5.25 | ND | ND | This study | |
| HL-79 | c.5603 G > A:p.Arg1868His | US | Het | 55 | 60 | DC | PrD | T | 1.048 | 4.8 | A = 0.0001/15 (ExAC) A = 0.0004/2 (1000 G) | A = 0.0005 (11/18868) | This study | |
| MYO7A (NM_000260) | HL-47 | c.4418 T > C:p.Phe1473Ser | US | Het | 257 | 60 | DC | PrD | D | 4.693 | 5.5 | ND | ND | This study |
| HL-47 | c.5472 C > G:p.Asn1824Lys | US | Het | 122 | 60 | DC | PrD | D | 1.98 | 3.49 | ND | ND | This study | |
| TMC1 (NM_138691) | HL-44 | c.604 C > G: p.Leu202Val | US | Het | 112 | 60 | DC | PrD | T | 1.871 | 5.78 | ND | ND | This study |
| HL-44 | c.616 A > T:p.Thr206Ser | US | Het | 110 | 60 | DC | PrD | T | 5.038 | 5.78 | ND | ND | This study | |
| ESPN (NM_031475) | HL-106 | c.1036 G > A:p.Glu346Lys | US | Het | 707 | 60 | DC | PrD | D | 4.523 | 3.77 | A = 0.00007/9 (ExAC) A = 0.0002/1 (1000 G) | A = 0.00009 (17/18870) | This study |
| HL-106 | c.1906T > C:p.Ser636Pro | US | Het | 23 | 24.8 | P | B | D | 1.289 | 5.1 | ND | ND | This study | |
| POU3F4 (NM_000307) | HL-78 | c.604 A > G:p.Lys202Glu | US | Hemi | 86 | 60 | D | PrD | NA | 4.676 | 5.31 | ND | ND | This study |
| MYH14 (NM_001145809) | HL-70 | c.1765A > C:p.Lys589Gln | US | Het | 270 | 60 | DC | PrD | D | 4.091 | 4.09 | C = 0.00002/2 (ExAC) | C = 0.000017, (2/111562) | This study |
| EYA1 (NM_000503) | HL-34 | c.1028 C > G: p.Ser343Cys | US | Het | (81/29) | (709/60) | DC | PrD | D | 5.842 | 5.86 | ND | ND | This study |
*Maximum minor allele frequency among all populations in gnomAD; DP, total depth; AD, alternative allele depth; Qual, SNP quality; MQ, mapping quality; LPa, likely pathogenic; Pa, pathogenic; US, uncertain significance; Het, Heterozygous; Hom, Homozygous; Hemi, Hemizygous; P, Polymorphism; DC, Disease causing; PrD, Probably damaging; PsD, Possibly damaging; D, Damaging; B, Benign; T, Tolerated; ND, not detected; NA, not applicable; PMID, PubMed ID (PMID is the unique identifier number used in PubMed.; PhyloP score from the Mutation Taster (http://www.mutationtaster.org/); in silico prediction Algorithm: Polyphen-2 (http://genetics.bwh.harvard.edu/pph2/index.shtml); SIFT (http://sift.jcvi.org/www/SIFT_chr_coords_submit.html); Conservation tools: GERP + + score in the UCSC Genome Browser (http://genome-asia.ucsc.edu/); ExAC, Exome Aggregation Consortium (http://exac.broadinstitute.org/); 1000 Genomes (https://www.ncbi.nlm.nih.gov/variation/tools/1000genomes/); GO-ESP, NHLBI GO Exome Sequencing Project (http://evs.gs.washington.edu/EVS/); GnomAD, genome Aggregation Database (http://gnomad.broadinstitute.org/).