TABLE 2.
Variants in the “Unsolved” (“Unsolved 1” and “Unsolved 2”) patients
| Gene | Unsolved | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| N | Transcript | Genotype | Chromosome | SIFT | Polyphen2 | ExAC database | Multiplex/simplex family | Zygosity | Unsolved 1/unsolved 2 | ACMG | |
| COL11A1 | 1 | NM_080630 | EX1_EX65 DUP | — | — | — | — | Simplex | Het | Unsolved 2 | VUS |
| DIAPH1 | 1 | NM_001079812 | c.2983C>T | chr5:140908277 | Damaging | — | — | Simplex | Het | Unsolved 2 | VUS |
| DIAPH3 | 1 | NM_001042517 | c.2608‐3T>C | chr13:60435673 | — | — | 0.00005802 | Simplex | Het | Unsolved 2 | VUS |
| 1 | NM_001042517 | c.3124C>T | chr13:60384961 | Damaging | Probably damaging | — | Multiplex | Het | Unsolved 2 | VUS | |
| 1 | NM_001042517 | c.1100G>A | chr13:60566632 | Damaging | Probably damaging | 0.00006994 | Simplex | Het | Unsolved 2 | VUS | |
| PDZD7 | 2 | NM_024895 | c.490C>T | chr10:102783245 | Damaging | Probably damaging | 0.00004959 | Simplex | Hom | Unsolved 1 | VUS |
| GJB2 | 1 | NM_004004 | c.109G>A | chr13:20763612 | — | Probably damaging | 0.006587 | Multiplex | Het | Unsolved 1 | Pathogenic |
| c.471G>A | chr13:20763250 | Tolerated | Benign | 0.000008261 | Het | VUS | |||||
| 1 | NM_004004 | c.235delC | chr13:20763486 | — | — | 0.0003625 | Simplex | Het | Unsolved 2 | Pathogenic | |
| ADGRV1 | 1 | NM_032119 | c.2241‐10A>T | chr5:89938443 | — | — | — | Simplex | Het | Unsolved 1 | Likely pathogenic |
| c.13637T>A | chr5:90079858 | Damaging | Possibly damaging | — | Het | VUS | |||||
| LOXHD1 | 1 | NM_144612 | c.1468C>T | chr18:44172511 | — | — | — | Multiplex | Het | Unsolved 1 | Pathogenic |
| c.977A>G | chr18:44181337 | Tolerated | — | 0.0003579 | Het | likely benign | |||||
| MT‐RNR1 | 1 | NC_012920 | m.681T>C | Simplex | Hom | Unsolved 1 | VUS | ||||
| MYH14 | 1 | NM_001077186 | c.475G>A | chr19:50720941 | Damaging | Probably damaging | 0.00001657 | Simplex | Het | Unsolved 2 | VUS |
| MYH9 | 1 | NM_002473 | c.1897C>T | chr22:36702600 | Tolerated | Benign | — | Multiplex | Het | Unsolved 2 | VUS |
| MYO15A | 1 | NM_016239 | c.9243_9251delinsAAGGGGGG | chr17:18062933..18062941 | — | — | — | Simplex | Het | Unsolved 1 | Pathogenic |
| c.3952G>A | chr17:18030399 | Damaging | Probably damaging | 0.000008324 | Het | VUS | |||||
| MYO1A | 1 | NM_005379 | c.235G>T | chr12:57441501 | Tolerated | Probably damaging | 0.002871 | Simplex | Het | Unsolved 2 | Likely benign |
| MYO6 | 1 | NM_004999 | c.2672C>T | chr6:76599787 | Damaging | Possibly damaging | 0.0001422 | Simplex | Het | Unsolved 2 | VUS |
| MYO7A | 1 | NM_000260 | c.1622C>T | chr11:76873966 | Damaging | Probably damaging | — | Simplex | Het | Unsolved 2 | VUS |
| 1 | NM_000260 | c.2558G>A | chr11:76890971 | Damaging | Probably damaging | — | Multiplex | Het | Unsolved 1 | VUS | |
| 2 | NM_000260 | c.1142C>T | chr11:76871270 | Tolerated | Possibly damaging | 0.000235 | Simplex | Het | Unsolved 2 | VUS | |
| 1 | NM_000260 | c.541C>T | chr11:76867776 | — | — | — | Simplex | Het | Unsolved 1 | Likely pathogenic | |
| NM_000260 | c.617G>A | chr11:76867932 | Damaging | Probably damaging | 0.00014 | Het | VUS | ||||
| OTOF | 1 | NM_194248 | c.1790C>T | chr2:26703667 | Tolerated | Possibly damaging | 0.000008474 | Simplex | Het | Unsolved 1 | VUS |
| c.829G>T | chr2:26717878 | Tolerated | Probably damaging | — | Het | VUS | |||||
| 1 | NM_194248 | c.1273C>T | chr2:26706449 | Damaging | Probably damaging | 0.00002 | Simplex | Het | Unsolved 1 | Pathogenic | |
| NM_194248 | c.3983G>C | chr2:26693501 | Damaging | Probably damaging | — | Het | VUS | ||||
| POU4F3 | 1 | NM_002700 | c.593G>A | chr5:145719583 | Damaging | Probably damaging | — | Simplex | Het | Unsolved 2 | VUS |
| 1 | NM_002700 | c.909G>T | chr5:145719899 | Simplex | Het | Unsolved 2 | VUS | ||||
| PTPRQ | 1 | NM_001145026 | c.1786A>G | chr12:80889054 | Damaging | Benign | — | Simplex | Het | Unsolved 2 | VUS |
| SLC17A8 | 1 | NM_139319 | c.760T>G | chr12:100795638 | Damaging | Probably damaging | — | Simplex | Het | Unsolved 2 | VUS |
| SLC26A4 | 1 | NM_000441 | c.919‐2A>G | chr7:107323898 | — | — | 0.0003058 | Multiplex | Het | Unsolved 1 | Pathogenic |
| c.290T>G | chr7:107303866 | Damaging | Probably damaging | — | Het | VUS | |||||
| 1 | c.1746 delG | chr7:107341584 | — | — | — | Simplex | Het | Unsolved 1 | Pathogenic | ||
| c.2110G>A | chr7:107350519 | Tolerated | Benign | — | Het | VUS | |||||
| 1 | c.2027T>A | chr7:107342495 | Damaging | Probably damaging | — | Simplex | Het | Unsolved 1 | Pathogenic | ||
| c.599A>G | chr7:107314792 | Damaging | Probably damaging | — | Het | VUS | |||||
| 1 | c.919‐2A>G | chr7:107323898 | — | — | 0.000306 | Multiplex | Het | Unsolved 2 | Pathogenic | ||
| TMC1 | 1 | NM_138691 | c.373A>C | chr9:75355045 | Tolerated | Benign | 0.00001654 | Simplex | Het | Unsolved 1 | VUS |
| c.1449A>C | chr9:75407151 | Tolerated | Possibly damaging | — | Het | VUS | |||||
| TRIOBP | 1 | NM_001039141 | c.1283C>G | chr22:38119846 | Damaging | Possibly damaging | 0.0001739 | Simplex | Het | Unsolved 1 | Likely benign |
| c.4442C>T | chr22:38130785 | Tolerated | Benign | 0.0001354 | Het | VUS | |||||
Specific candidate pathogenic variants in “Unsolved” patients of multiplex families (in bold).
“Exac Database,” Exome Aggregation Consortium (ExAC) database.
Abbreviations: ACMG, a technical standard of the American College of Medical Genetics and Genomics; unsolved1, deafness patients in unsovled1 group. In this group, deafness patients harbored candidate pathogenic variants that could possibly explain their pathology; unsolved2, deafness patients in unsovled2 group. In this group, deafness patients harbored the candidate pathogenic variants that could not explain their pathology; VUS, variant of unknown significance; likely benign, variant of likely benign.