Table 3.
Ten most commonly identified genetic variants causing deafness
| Gene | Variant | Diagnostic frequency (n alleles) | % of diagnosed variants |
|---|---|---|---|
| MORL | |||
| STRC | CNV—partial/whole-gene deletion | 84 | 11.8% |
| GJB2 | c.35delG, p.Gly12fs | 51 | 7.1% |
| GJB2 | c.109G>A, p.Val37Ile | 27 | 3.8% |
| GJB2 | c.101T>C, p.Met34Thr | 20 | 2.8% |
| OTOA | CNV—partial/whole-gene deletion | 7 | 1.0% |
| USH2A | c.4714C>T, p.Leu1572Phe | 7 | 1.0% |
| USH2A | c.2299delG, p.Glu767fs | 7 | 1.0% |
| SLC26A4 | c.1001+1G>A | 6 | 0.8% |
| GJB2 | c.167delT, p.Leu56fs | 5 | 0.7% |
| MYO7A | c.3719G>A, p.Arg1240Gln | 4 | 0.6% |
| MORL total | 218 | 30.5% | |
| LMM | |||
| GJB2 | c.35delG, p.Gly12fs | 196 | 14.3% |
| GJB2 | c.109G>A, p.Val37Ile | 131 | 9.6% |
| STRC | CNV—partial/whole-gene deletion | 110 | 8.0% |
| GJB2 | c.101T>C, p.Met34Thr | 49 | 3.6% |
| USH2A | c.2299delG, p.Glu767fs | 38 | 2.8% |
| GJB2 | c.167delT, p.Leu56fs | 17 | 1.2% |
| GJB2 | c.−23+1G>A | 13 | 1.0% |
| GJB2 | c.269T>C, p.Leu90Pro | 13 | 1.0% |
| GJB2 | c.313_326del, p.Lys105fs | 11 | 0.8% |
| GJB2 | GJB6-deletion upstream | 10 | 0.7% |
| LMM total | 588 | 43.0% |
Ten variants most commonly identified as causes of deafness in two clinical testing laboratories: Molecular Otolaryngology & Renal Research Labs (MORL, Iowa City, IA) and the Laboratory for Molecular Medicine (LMM, Cambridge, MA). MORL data are from 2460 individuals from the US population with deafness who presented for diagnostic comprehensive genetic testing with the OtoSCOPE platform. The total number of diagnoses provided is 982, or 39.9% of 2460. All ethnicities are included and no exclusions were made based on type of deafness (R.J.S., unpublished data). LMM data are from 737 diagnosed cases mainly from the US population with deafness who presented for diagnostic genetic testing at the LMM. GJB2-related deafness was overrepresented because 104 cases were only tested for GJB2 including deletions of 5’ upstream regulatory regions involving GJB6. Data from MORL are adapted from Sloan-Heggen et al. (2016);13 data from LMM are unpublished (contributed by S.A. and J.S.).
CNV copy-number variant.