Table 2. Characteristics of the novel variants in the GJB2 gene.

Variant	Protein effect	Affected protein domain	Pathogenicitya	Pathogenic criteriaa	Genotype, number of family members with genotype	Severity of hearing loss	Ethnicity
c.94C>G	Missense	TM1	Likely pathogenic	PM2,3,5+PP1,2,3	c.[35delG]+[94C>G], 2	Moderately severe, severe	Tatar
c.205T>C	Missense	EC1	Likely pathogenic	PM2,3+PP2,3	c.[35delG]+[205T>C], 1	Severe	Unknown
c.245T>A	Missense	TM2	Likely pathogenic	PM2,3,5+PP2,3	c.[35delG]+[245T>A], 1	Severe	Tatar/Russian
c.266T>C	Missense	TM2	Likely pathogenic	PM2,3+PP1,2,3	c.[35delG]+[266T>C], 2	Severe	Russian
					c.[109G>A]+[266T>C], 1	Severe to profound	Russian
c.399G>A	Nonsense	TM3	Pathogenic	PVS1+PS1+PM2+PP3	c.[35delG]+[399G>A], 1	Unknown	Russian
c.402G>A	Nonsense	TM3	Pathogenic	PVS1+PS1+PM2,3,5+PP3	c.[35delG]+[402G>A], 1	Severe	Tajik
c.502_601del10	Frameshift	EC2	Pathogenic	PVS1+PM2,3+PP3	c.[35delG]+[502_601del10], 1	Severe	Russian
c.532G>A	Missense	EC2	Likely pathogenic	PM2,3,5+PP2,3	c.[35delG]+[457G>A,532G>A]b, 1	Severe to profound	Russian

^aPathogenicity was evaluated according to the ACMG guidelines for classifying pathogenic variants.²⁷ Each pathogenic criterion is weighted as very strong (PVS1), strong (PS1–4), moderate (PM1–6) or supporting (PP1–5).²⁷

^bc.457G>A is rare neutral polymorphism (rs111033186).