Table 1 Results from whole-exome sequencing of a sample of the index patient, IV:2

From: A C-terminal nonsense mutation links PTPRQ with autosomal-dominant hearing loss, DFNA73

Gene

Isoform

cDNA

Protein

Zygosity

rs ID

Clin. assoc.

Ref.

Funct. pred.

Cons. pred.

TGP AF (%)

ESP AF (%)

ExAC AF (%)

% Covered

Filter 1: variants located in mapped candidate region on chromosome 12 (78,839,926 (rs10860423)–93,458,831 (rs1542481))

 LRRIQ1

NM_001079910.1

c.4948delA

p.Met1650*

het.

rs763597988

—

—

—

—

—

—

0.00083

88.40

 PTPRQ

NM_001145026.1

c.6881G>A

p.Trp2294*

het.

—

—

—

3/3

4/4

—

—

—

94.42

 SYT1

NM_005639.2

c.1258G>A

p.Val420Ile

het.

rs61756211

—

—

1/10

2/6

—

0.12

0.32 (1 × hom)

100.00

 TMTC2

NM_152588.1

c.1141G>A

p.Val381Ile

het.

rs35725509

—

—

1/10

1/6

1.16

0.55

1.12 (24 × hom)

98.88

Filter 3: Variants in genes reportedly associated with hearing impairment (HGMD keywords: hearing, deafness)

 PTPRQ

NM_001145026.1

c.6365G>A

p.Trp2122*

het.

—

—

—

3/3

4/4

—

—

—

94.42

 COL9A3

NM_001853.3

c.1427C>G

p.Pro476Arg

het.

rs142066316

—

—

7/10

6/6

0.16

0.3

0.18 (3 × hom)

93.75

 RDX

NM_002906.3

c.1412C>A

p.Pro471His

het.

rs754733997

—

—

4/10

6/6

—

—

0.00082

89.90

 RDX

NM_002906.3

c.1557G>C

p.Gln519His

het.

rs761349279

—

—

6/10

4/6

—

—

0.00082

89.90

 MYH7B

NM_020884.4

c.772G>A

p.Gly258Arg

het.

—

—

—

5/10

6/6

—

—

—

98.80

 TSPEAR

NM_144991.2

c.88C>T

p.Arg30Cys

het.

rs138759270

—

—

4/9

6/6

—

0.05

0.02

100.00

 LOXHD1

NM_144612.6

c.2575C>T

p.Arg859Trp

het.

rs372546084

—

—

7/10

4/6

0.02

0.02

0.02

99.93

 KCNE1

NM_000219.5

c.139G>A

p.Val47Ile

het.

rs199473353

Yes

—

1/7

1/6

0.1

—

0.01

99.02

 MYO15A

NM_016239.3

c.1111C>A

p.Pro371Thr

het.

rs200382813

—

—

4/9

1/6

0.04

0.23

0.14

98.79

 GJB2

NM_004004.5

c.109G>A

p.Val37Ile

het.

rs72474224

Yes

36

5/10

4/6

1.54

0.13

0.66 (39 × hom)

94.86

 PNKP

NM_007254.3

c.58C>T

p.Pro20Ser

het.

rs3739168

—

37

1/10

5/6

0.66

0.9

0.76 (6 × hom)

100.00

 PNKP

NM_007254.3

c.1127-8C>T

—

het.

rs3739203

—

—

—

—

0.54

0.92

0.72 (7 × hom)

100.00

 USH2A

NM_206933.2

c.688G>A

p.Val230Met

het.

rs45500891

Yes

38

1/9

0/6

1.02

1.59

1.55 (18 × hom)

99.53

 USH2A

NM_206933.2

c.7685T>C

p.Val2562Ala

het.

rs56385601

Yes

—

2/10

4/6

0.48

0.65

0.65 (8 × hom)

99.53

 GJB3

NM_024009.2

c.94C>T

p.Arg32Trp

het.

rs1805063

—

39

9/10

5/6

1.3

2.31

2.42 (56 × hom)

100.00

  1. AF, allele frequency; cDNA, complementary DNA; Clin. assoc., SNPs annotated as “clinically associated”; covered, percentage of nucleotides of the gene that are covered at least 15 × ; Cons. pred., assessment of conservation by PhyloP, GERP++, PhastCons, SiPhy, Grantham Distance and BLOSUM62; ESP, Exome Sequencing Project; ExAC, Exome Aggregation Consortium; Funct. pred., functional predictions by SIFT, PolyPhen-2, MutationTaster, MutationAssessor, FATHMM, LRT, VEST, CADD, PROVEAN, and DANN; het, heterozygous; HGMD, Human Gene Mutation Database; hom, number of healthy ExAC individuals who are homozygous for the respective variant; Isoform, RefSeq accession number of the reported isoform; rs ID, rs number according to dbSNP build 144; TGP, 1000 Genomes Project.
  2. The upper part (filter 1) lists variants, including the PTPRQ nonsense mutation, located in the chromosomal candidate region identified via genome-wide linkage analysis. filter 3 (lower part) analyzed for variants in genes knowingly associated with inherited hearing impairment.
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