Table 3.
Mutations and genotypes found in the SLC26A4 gene
| SLC26A4 mutations | dbSNP | na | ClinVar status | Pathogenicity scoresb | Compound heterozygosity | Double heterozygosity | DFNB4 associationc | |||
|---|---|---|---|---|---|---|---|---|---|---|
| GJB2 | GJB6 | MT-RNR1 | OR (95%CI) | p value | ||||||
| c.-66C>G | rs17154282 | 13 | Benign/Likely benign | 2 (FunSeq) 4 (RegulomeDB) |
c.-103T>C; p.Asn324Tyr; p.Val609Gly | c.35delG/wt; c.35delG/c.35delG | D13S1854 | ND | 0.33 (0.09–1.05) | p = 0.03684 |
| c.-103T>C | rs60284988 | 1 | Conflicting interpretations of pathogenicity | 2 (FunSeq) 5 (RegulomeDB) 17.77 (CADD) |
c.-66C>G | ND | ND | ND | ||
| p.Gly5Gly | rs7811324 | 1 | Benign | 1.00 (Sift) 22.4 (CADD) |
– | ND | ND | ND | ||
| p.Ala189Ser | rs35045430 | 1 | Benign | 0.00 (Sift) 1.000 (PolyPhen-2) 13.12 (CADD) |
– | ND | ND | ND | ||
| p.Ile254Val | – | 1 | – | 0.62 (Sift) 0.939 (PolyPhen-2) 23.4 (CADD) |
– | ND | ND | ND | – | p = 0.3052 |
| p.Ile300Leu | rs111033304 | 3 | Benign/Likely benign | 0.00 (Sift) 0.972 (PolyPhen-2) 28.5 (CADD) |
– | ND | ND | ND | ||
| p.Asn324Tyr | rs36039758 | 2 | Benign/Likely benign | 0.01 (Sift) 0.997 (PolyPhen-2) 26.5 (CADD) |
c.-66C>G | ND | ND | ND | ||
| p.Asn382Lys | – | 1 | – | 0.00 (Sift) 1.000 (PolyPhen-2) 31.0 (CADD) |
– | ND | ND | ND | – | p = 0.3052 |
| p.Leu597Ser | rs55638457 | 1 | Benign/Likely benign | 0.00 (Sift) 0.999 (PolyPhen-2) 29.3 (CADD) |
– | c.35delG/c.35delG | ND | ND | ||
| p.Val609Gly | rs17154335 | 5 | Benign/Likely benign | 0.54 (Sift) 0.000 (PolyPhen-2) 18.12 (CADD) |
c.-66C>G | p.Val27Ile/wt | ND | ND | ||
“/wt” means the presence of a wild type allele, i.e. when the mutations were found in heterozygosis
a“n” represents the number of individuals affected by the mutation
bThe scores will differ from tool to tool. Sift: the mutations are considered as pathogenic when scores ≤ 0.05; PolyPhen-2: the amino acid substitution is considered pathogenic when scores > 0.5; CADD: the mutations are considered pathogenic when PHRED score > 20. FunSeq: scores range from 0 to 6 and as high as the most deleterious. RegulomeDB: scores range from 1a to 6, “1a” harboring the highest number of evidences for each related activity
cThe analysis of association was performed only for those three mutations. The OR values were calculated in comparison to the frequency of those mutations on the control group, using Fisher’s Exact Test. The p-values were accessed using Pearson’s Chi squared test, both performed by R Commander tool
ND no mutation detected