Table 1.
Heterozygous Variants and their predicted consequences detected after Sanger in both samples (pedigrees with microsatellite segregation compatible with linkage to SLC26A4 and individuals presenting cochlear-vestibular malformations)
| Cohort | Patient | Nucleotide | Protein | Location | Deafness variation database | SIFT (score), PolyPhen2 (score), MutationTaster (score), Splice Prediction Tools | 1000 g | ESP6500 | Conclusion (According to ACMG criteria) | Genotype | Protein locationb |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Families with autosomal recessive inheritance | 6 | c.1003 T > G a | p.F335V a | exon 9 | – | Damaging (0.003), Probably damaging (0.99), Disease causing (0.99) | – | – | likely pathogenic | Compound heterozygosis | External loop |
| c.1553G > A a | p.W518X a | exon 14 | – | -, −, Disease causing (1) | – | – | pathogenic | C-terminal | |||
| 7 | c.15C > A | p.G5G | exon 2 | benign | – | 0.006 | 0.005 | benign | – | – | |
| IVS10 + 35G > T | – | intron 10 | benign | – | 0.003 | 0.003 | benign | – | – | ||
| 24 | c.84C > A | p.S28R | exon 2 | Likely Pathogenic | Damaging (0.003), Possibly damaging (0.92), Polymorphism (0.79) | 0 | 0 | likely pathogenic | Compound heterozygosis | N-terminal | |
| IVS19 + 2 T > C a | SS a | intron 19 | – | -, −, Disease causing (1), splice donor site abolished | – | – | pathogenic | C-terminal | |||
| 44 | c.218A > G | p.E73G | exon 3 | – | Tolerated (0.313), Benign (0.00), Disease causing (0.77) | – | – | benign | – | – | |
| IVS15-18 T > A | – | intron 15 | benign | – | 0.013 | 0.02 | benign | – | – | ||
| 51 | IVS15 + 76G > C | – | intron 15 | benign | – | 0.039 | 0 | benign | – | – | |
| c.1826 T > G | p.V609G | exon 17 | benign | Tolerated (0.54), Benign (0.00), Polymorphism (0.19) | 0.04 | 0.049 | benign | – | – | ||
| c.2130C > T | p.D710D | exon 19 | benign | – | 0.019 | 0.023 | benign | – | – | ||
| c.2218G > A | p.G740S | exon 19 | benign | Tolerated (0,091), Benign (0.00), Polymorphism (0.99) | 0.015 | 0.017 | benign | – | – | ||
| Cases of deafness with suspected PS and/or presenting EVA or other cochleovestibular malformation | 71 | c.1246A > C | p.T416P | exon 10 | Pathogenic | Damaging (0.00), Probably damaging (1.00), Disease causing (0.99) | 0 | 0 | likely pathogenic | Heterozygosis (monoallelic) | TM10/Cytosolic Interface |
| 76 | c.898A > C | p.I300L | exon 7 | benign | Damaging (0.02), Probably damaging (0.97), Disease causing (0.99) | 0.005 | 0.004 | benign | – | – | |
| 78 | IVS8-143 T > C | intron 8 | – | – | – | – | benign | – | – | ||
| 83 | IVS7 + 2 T > C | SS | intron 7 | Pathogenic | -, −, Disease causing (1) | 0 | 0 | pathogenic | Heterozygosis (monoallelic) | TM7 | |
| 85 | IVS15-18 T > A | – | intron 18 | benign | – | 0.013 | 0.022 | benign | – | – |
In bold, variants considered as pathogenic or likely pathogenic
a indicates variants reported for the first time in this study. bAccording to Bassot et al. 2017 [52]