Contribution of SLC26A4 to the molecular diagnosis of nonsyndromic prelingual sensorineural hearing loss in a Brazilian cohort

Table 3 Mutations and genotypes found in the SLC26A4 gene

SLC26A4 mutations	dbSNP	n^a	ClinVar status	Pathogenicity scores^b	Compound heterozygosity	Double heterozygosity			DFNB4 association^c
SLC26A4 mutations	dbSNP	n^a	ClinVar status	Pathogenicity scores^b	Compound heterozygosity	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

ISSN: 1756-0500