Table 4 Characteristics of hearing cases with biallelic GJB2 variants involving p.Met34Thr or p.Val37Ilele, including homozygotes and compound heterozygotes with another pathogenic or likely pathogenic variant

From: Consensus interpretation of the p.Met34Thr and p.Val37Ile variants in GJB2 by the ClinGen Hearing Loss Expert Panel

Genotype

[Met34Thr]; [P/LP]

[Met34Thr]; [Met34Thr]

[Met34Thr]; [Val37Ile]

[Met34Thr]; [PTC]

[Val37Ile]; [P/LP]

[Val37Ile]; [Val37Ile]

[Val37Ile]; [PTC]

c.[35delG]; [35delG]a

Total probands

138

27

17

78

131

139

78

86

Total with characterizationb

183

28

17

86

127

150

91

86

Age of onsetc

177

28

17

83

139

144

78

86

 Childhood (<18 years)

155 (88%)

23 (82%)

16 (94%)

72 (87%)

113 (81%)

120 (83%)

50 (64%)

84 (98%)

Laterality

133

21

11

62

109

111

66

86

 Unilateral

4 (3%)

0

1 (9%)

2 (3%)

5 (5%)

4 (4%)

3 (5%)

0 (0%)

 Bilateral

129 (97%)

21 (100%)

10 (99%)

60 (97%)

104 (95%)

107 (96%)

63 (95%)

86 (100%)

 Asymmetrical

15 (12%)

3 (27%)

2 (20%)

9 (15%)

6 (6%)

7 (7%)

1 (2%)

0 (0%)

Frequency rangesd

66

14

6

30

59

59

34

1

 High

41 (62%)

9 (64%)

5 (83%)

13 (43%)

35 (59%)

41 (69%)

21 (62%)

1 (100%)

 Mid

17 (26%)

4 (29%)

1 (17%)

11 (37%)

3 (5%)

10 (17%)

2 (6%)

0 (0%)

 Low

0 (0%)

0 (0%)

0 (0%)

0 (0%)

7 (12%)

0 (0%)

6 (18%)

0 (0%)

Progression

20 (11%)

2 (7%)

4 (24%)

10 (12%)

20 (16%)

10 (7%)

13 (14%)

4 (4%)

Severity

146

24

14

63

121

133

77

63

 Mild

55 (38%)

10 (42%)

5 (36%)

26 (41%)

29 (24%)

48 (36%)

23 (30%)

0 (0%)

 Moderate

67 (46%)

8 (33%)

7 (50%)

29 (46%)

55 (45%)

52 (39%)

34 (44%)

7 (11%)

 Mild+Moderate

122 (84%)

18 (75%)

12 (86%)

55 (87%)

84 (69%)

90 (75%)

57 (74%)

7 (11%)

 Moderately severe

12 (8%)

3 (13%)

2 (14%)

3 (5%)

20 (17%)

12 (9%)

9 (12%)

9 (14%)

 Severe

4 (3%)

0 (0%)

0 (0%)

3 (5%)

16 (13%)

20 (15%)

10 (13%)

9 (14%)

 Profound

8 (5%)

3 (13%)

0 (0%)

2 (3%)

1 (1%)

1 (1%)

1 (1%)

38 (60%)

Statistics (OR [95% CI], p)e

        

 [Met34Thr];[Val37Ile]

 

0.86 [0.0–673], 0.97

      

 [Met34Thr];[PTC]

 

0.76 [0.02–34], 0.89

0.88 [0.0–281], 0.97

     

 [Val37Ile];[Val37Ile]

 

1.35 [0.04–49], 0.87

1.56 [0.0–432], 0.88

1.77 [0.47–7.7], 0.40

    

 [Val37Ile];[PTC]

 

1.36 [0.04–57], 0.87

1.00 [0.34–3.00], 0.88

1.78 [0.33–9.4], 0.50

 

1.00 [0.34–3.00], 0.99

  

 c.[35delG];[35delG]

 

79 [1.5–4210], 0.0315

91 [0.3–32548], 0.13

103 [11–902],<0.0001

 

58 [10–336],<0.0001

58 [7.7–438],<0.0001

 
  1. Statistically significant differences in severity are in bold.
  2. Italic values show the skewed enrichment of mild/mod HL in V37I/M34t genotypes compared to 35delG.
  3. CI confidence interval, OR odds ratio, [P/LP] a pathogenic or likely pathogenic allele in GJB2, [PTC] an allele with a premature termination codon in GJB2.
  4. aData on c.35delG cases were from the Laboratory for Molecular Medicine only.
  5. bAll information is not available for all individuals.
  6. cWhen age of onset was not available, age of testing was used as a surrogate.
  7. dFlat audiogram shapes that affect all frequency ranges are underreported.
  8. eOdds ratio refers to the genotype in the column header more likely to be milder than that in the row header.
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