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MutTaster. MutAssessor. FATHMM. RadialSVM. LR. VEST3. CADD. GERP++ .... Comment of variant interpretation. 2120. 4 ... prediction score and ClinVar status.
Supp. Figure S1 Screen shots of the case viewer. The case viewer is an interface for the unified management of detailed patient clinical information and variant information obtained from next-generation sequencing analysis. The variant list is automatically filtered from a large number of identified variants to the selected candidate variant.

Clinical NGS Database ver. 1.2 Sample list

Panel Info

Case viewer

Variant list

Variant viewer Report maker

Annotation

Patohgenic

Control

Search

Browse

Import VCF

Sort

DB update

Export

Annotation Import

Send E-mail

Case_Viewer

ID

Family_NUM

Demo10

Clinical information

project_NUM

DemoData

relationship

JHLB0001

Diagnosis

project

Fam001

proband_ID

Clinical diagnosis

ShinshuMP1

proband

AD/Mit

Onset_Age

Congenital sensorineural hearing loss

hereditary

sampling_date AR/Spo

X_linked

Control

Genotype

Curation_date

homozygote

Comment of NGS analysis

40

Category_Data_1

YES

NO

N/A

Numerical_Data_1

Category_Data_2

YES

NO

N/A

Numerical_Data_2

Numerical_Data_22

Category_Data_3

YES

NO

N/A

Numerical_Data_3

Numerical_Data_23

Category_Data_4

YES

NO

N/A

Numerical_Data_4

Numerical_Data_24

Category_Data_5

YES

NO

N/A

Numerical_Data_5

Numerical_Data_25

Category_Data_6

YES

NO

N/A

Numerical_Data_6

Numerical_Data_26

Category_Data_7

YES

NO

N/A

Numerical_Data_7

Numerical_Data_27

Category_Data_8

YES

NO

N/A

Numerical_Data_8

Numerical_Data_28

Category_Data_9

YES

NO

N/A

Numerical_Data_9

Numerical_Data_29

Category_Data_10

YES

NO

N/A

Numerical_Data_10

Numerical_Data_30

Category_Data_11

YES

NO

N/A

Numerical_Data_11

Numerical_Data_31

Category_Data_12

YES

NO

N/A

Numerical_Data_12

Numerical_Data_32

Category_Data_13

YES

NO

N/A

Numerical_Data_13

Numerical_Data_33

Category_Data_14

YES

NO

N/A

Numerical_Data_14

Numerical_Data_34

Category_Data_15

YES

NO

N/A

Numerical_Data_15

Numerical_Data_35

Category_Data_16

YES

NO

N/A

Numerical_Data_16

Numerical_Data_36

Category_Data_17

YES

NO

N/A

Numerical_Data_17

Numerical_Data_37

Category_Data_18

YES

NO

N/A

Numerical_Data_18

Numerical_Data_38

Category_Data_19

YES

NO

N/A

Numerical_Data_19

Numerical_Data_39

Category_Data_20

YES

NO

N/A

Numerical_Data_20

Numerical_Data_40

Curator

Diagnostic candidate: Diagnosis: OTOF

Numerical_Data

Categorical Data

medical_history

Causative gene

Gender Female

center_name Shinshu-university

Unknown

Imaging_Data1

Family_History

0

registration_date

Numerical_Data_21

Imaging_Data 2

Imaging_Data 3

Imaging_Data 4

Imaging_Data 5

Clinvar Database Information

NGS results (auto filtering)

Previously Reported Variants Information Ref.Seq. ID

Exon

AD

AR

ESPN

NM_031475

exon13

c.C2513A

p.A838E

het

0.548

10.3

Variant View

0

1

0

0

0

Confirmed

SeqError

YES

NO

.

.

.

USH2A

NM_206933

exon34

c.T6506A

p.I2169K

het

0.167

37.2

Variant View

0

1

0

0

0

Confirmed

SeqError

YES

NO

.

.

.

CDH23

NM_022124

exon36

c.C4762T

p.R1588W

het

0.557

10.6

Variant View

0

1

0

0

0

Confirmed

SeqError

YES

NO

.

.

.

MYH14

NM_001145

exon2

c.58_59insC

p.V20fs

het

0.500

9.1

Variant View

0

1

0

0

0

Confirmed

SeqError

YES

NO

MYH14

NM_001145

exon35

c.A4799G

p.N1600S

het

0.520

9.2

Variant View

0

1

0

0

0

Confirmed

SeqError

YES

NO

.

.

.

OTOF

NM_194323

exon29

c.G3515A

p.R1172Q

hom

1.000

38.0

Variant View

0

7

0

0

0

Confirmed

SeqError

YES

NO

.

.

.

DFNB31

NM_001083

exon6

c.G200A

p.R67H

het

0.486

8.0

Variant View

0

1

0

0

0

Confirmed

SeqError

YES

NO

unknown

not_specifie

single

Base Change

AA Change

genotype AFforGT QD

Control DB Allele Freq.

Gene symbol

CNT

X-link UNK

Pathogenicity

AR_Pathogenic

DirectSeq.

Segregation

pathogenicity

disease

pmid

AlleleFreq1

AlleleFreq2

pathogenicity

disease

submitter

All Rights Reserved 2015. Shinshu University School of Medicine Department of Otorhinolaryngology.

Supp. Figure S2 Screen shots of the variant viewer. The variant viewer is an interface for accessing all knowledge regarding the variant, including the phenotypes of the variant carriers and inheritance mode-specific odds ratios. It is also useful for managing the list of patients carrying the same variant and assists in enabling time-efficient browsing of these patients.

Clinical NGS Database ver. 1.2 Sample list

Panel Info

Case viewer

Variant list

Variant viewer Report maker

Annotation

Patohgenic

Control

Search

Browse

Sort

Import VCF

DB update

Export

Annotation Import

Send E-mail

Chr chr2

Start

End

Ref

Alt

26681086

26681086

C

T

Pathogenicity

Func. refgene Gene refgene exonic;

Curation_Date

OTOF

GeneDetail

Exonic Func

.

nonsynonymo Entrez_gene_ID 9381

Curator

AR_Pathogenic

CNT_alt#

Comment of variant interpretation

CNT_ref#

4

Genotype DP

GQ

Project

Hereditaly

Enrichment

OR_AD/Mit_95%CI

0.7

0.1

het

549

99

Iowa

AR/Spo

Panel_1

Case_Preview

260

het

999

99

hokenMP19

AR/Spo

Panel_1

Case_Preview

261

het

755

99

hokenMP19

AR/Spo

Panel_1

Case_Preview

262

het

260

99

hokenMP19

AR/Spo

Panel_1

Case_Preview

2703

hom

432

99

Iowa

AR/Spo

Panel_1

Case_Preview

2958

het

127

99

shinshuCIPtMP1

AR/Spo

Panel_1

Case_Preview

3354

het

404

99

Iowa

Unknow

Panel_1

Case_Preview

4006

het

370

99

Iowa

AD/Mit

Panel_1

Case_Preview

4879

het

445

99

SenshinMP1

AR/Spo

Panel_1

Case_Preview

Sample# AveDepth Ref#

.002743484

729

afr

1000G

?

ESP6500

.

37.57

amr

.

all

1.000000

D

1454

eas

.

0.001

Alt# 4

eur

sas

.

.

AD

2

/ 1532

0.00131

SIFT

AR

48

/ 4298

0.01117

PP2 HDIV

0

/

?

X_link

0

PP2 HVAR

UNK

14

/ 1468

0.00954

aa

ea

CNT

0

/ 666

0.00000

.

.

Case

64

/

0.00877

7298

2.59E-05

ExAC03

2.2

afr

amr

eas

fin

nfe

0

0

0.0006

0

0

oth 0

D

D

.

D

.

D

1

D

FATHMM 0.457

D

GERP++

0.994

D

RadialSVM 0.631

D

PhyloP46 0.871

LR 0.762

D

PhyloP100 0.927

LRT

.

variant_locate

. D COSMIC_ID

.

MutAssessor

VEST3 0.831

disease

4.8

SiPhy29 17.465

COSMIC_DIS

GWAS_DIS

. GWAS_P

. GWAS_OR

ClinVar_DB ClinVar_DBID .

.

GWAS_BETA GWAS_PMID GWAS_SNP

pmid

AF1

AR 48

X_link 0

CNT 0

UNK 14 N

±

Y

Category_Data_1

Category_Data_11

Category_Data_2

Category_Data_12

Category_Data_3

Category_Data_13

Category_Data_4

Category_Data_14

Category_Data_5

Category_Data_15

Category_Data_6

Category_Data_16

Category_Data_7

Category_Data_17

Category_Data_8

Category_Data_18

Category_Data_9

Category_Data_19

Category_Data_10

Category_Data_20

N

± Y

PS2: De novo (both parents confirmed) in a patient w/o no family history PS3: Well established experiment support damaging effect PS4: The prevalence of the variant in affected individuals is significantly high (OR > 5.0) PM1: Located in a mutational hot spot and/or well-established functional domain PM2: Absent from controls (or at extremely low frequency if recessive) PM3: For recessive disorder detected in trans with a pathogenic variant PM4: Protein length changes (in-frame deletions/insertions) in a nonrepeat region or stop-loss variants PM5: Novel missense change at same AA position of other pathogenic variant PM6: Assumed de novo, but without both parents confirmation PP1: Cosegregation with disease in multiple affected family members

Upgrade PM7

N

Y

Category_Data_1

Category_Data_11

Category_Data_2

Category_Data_12

Category_Data_3

Category_Data_13

Category_Data_4

Category_Data_14

Category_Data_5

Category_Data_15

Category_Data_6

Category_Data_16

Category_Data_7

Category_Data_17

Category_Data_8

Category_Data_18

Category_Data_9

Category_Data_19

Category_Data_10

Category_Data_20

N

PS5

PP2: Missense variant in a gene that has a low rate of benign missense variation PP3: Multiple lines of computational evidence support a deleterious effect PP4: Patient’s phenotype or family history is highly specific for a disease with a single genetic etiology PP5: Reputable source recently reports variant as pathogenic BA1: Allele frequency is >5% in ESP, 1000 Genomes, or ExAC BS1: Allele frequency is greater than expected for disorder BS2: Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous) BS3: Well established experiment show no damage effect

BP2: Observed in trans with a pathogenic variant for a fully penetrant dominant gene/disorder or observed in cis with a pathogenic variant in any inheritance pattern

Numerical_Data_1

±

Numerical_Data_15

±

Numerical_Data_29

±

Numerical_Data_2

±

Numerical_Data_16

±

Numerical_Data_30

±

Numerical_Data_3

±

Numerical_Data_17

±

Numerical_Data_31

±

Numerical_Data_4

±

Numerical_Data_18

±

Numerical_Data_32

±

Numerical_Data_5

±

Numerical_Data_19

±

Numerical_Data_33

±

Numerical_Data_6

±

Numerical_Data_20

±

Numerical_Data_34

±

Numerical_Data_7

±

Numerical_Data_21

±

Numerical_Data_35

±

Numerical_Data_8

±

Numerical_Data_22

±

Numerical_Data_36

±

Numerical_Data_9

±

Numerical_Data_23

±

Numerical_Data_37

±

Numerical_Data_10

±

Numerical_Data_24

±

Numerical_Data_38

±

Numerical_Data_11

±

Numerical_Data_25

±

Numerical_Data_39

±

Numerical_Data_12

±

Numerical_Data_26

±

Numerical_Data_40

±

Numerical_Data_13

±

Numerical_Data_27

±

Numerical_Data_14

±

Numerical_Data_28

±

Numerical_Data_1

±

Numerical_Data_15

±

Numerical_Data_29

±

Numerical_Data_2

±

Numerical_Data_16

±

Numerical_Data_30

±

Numerical_Data_3

±

Numerical_Data_17

±

Numerical_Data_31

±

Numerical_Data_4

±

Numerical_Data_18

±

Numerical_Data_32

±

Numerical_Data_5

±

Numerical_Data_19

±

Numerical_Data_33

±

Numerical_Data_6

±

Numerical_Data_20

±

Numerical_Data_34

±

Numerical_Data_7

±

Numerical_Data_21

±

Numerical_Data_35

±

Numerical_Data_8

±

Numerical_Data_22

±

Numerical_Data_36

±

Numerical_Data_9

±

Numerical_Data_23

±

Numerical_Data_37

±

Numerical_Data_10

±

Numerical_Data_24

±

Numerical_Data_38

±

Numerical_Data_11

±

Numerical_Data_25

±

Numerical_Data_39

±

Numerical_Data_12

±

Numerical_Data_26

±

Numerical_Data_40

±

Numerical_Data_13

±

Numerical_Data_27

±

Numerical_Data_14

±

Numerical_Data_28

±

Averaged clinical data of the patients caused by this gene mutations

Averaged Onset Age

PVS1: null variant in a gene where LOF is a known mechanism of disease PS1: Same amino acid change as a previously established pathogenic variant

BP3: In frame deletion/insertion in repetitive region without known function

Averaged Onset Age

Y

Pathogenic

BP1: Missense variant in a gene for which primarily truncating variants are known to cause disease

AF2

NULL

Averaged clinical data of the variant carriers AD 2

ACMG_clasification:

BS4: Lack of segregation in affected members of a family

NM_194323:c.3515G>A

NM_194323:p.Arg1172Gln NULL

2.493

CADD

base_change

aa change

OTOF

Unknown

D

D

ClinVar_SIG ClinVar_DIS ClinVar_STATUS ClinVar_ID

pathogenicity

D

sas 0

Pathogenicity data from Previously Reported Variant Database gene

- 16.6

0.000172

p-value

0.997

MutTaster 1 dbSNP

all

OR_AR/Spo_95%CI

6.0

in silico prediction

Freq

all

OR_AR/Spo

- 3.8

DirectSeq. Segregation

2529

CNT_DB

AA Change p.R1172Q

BP4: Multiple lines of computational evidence suggest no impact on gene BP5: Variant found in a case with an alternate molecular basis for disease BP6: Reputable source recently reports variant as benign BP7: A synonymous (silent) variant for which splicing prediction algorithms predict no impact

ACMG variant clasification

Allele frequencies in public and in house database

OR_AD/Mit

p-value

ID

Base Change c.3515G>A

in silico prediction score and ClinVar status

Averaged clinical information who carried same variant

Exon exon29

2120

Allele Frequency Information

Averaged clinical information of the patient caused by same gene

Ref.Seq. ID NM_194323

AAChange "OTOF:NM_194323:exon29:c.3515G>A:p.R1172Q,OTOF:NM_001287489:exon46:c.5816G>A:p.R1939Q"

Odds ratio

Patient list who Variant carring same mutation interpretation

Variant_Viewer

Supp. Table S1. Previously reported pathogenic variants identified in 3,719 Japanese hearing loss patients. Supplemental Table S1. Previously reported pathogenic variants identified in 3,719 Japanese hearing loss patients. Chr 17

Start* 79478023

End* 79478023

Ref A

Alt G

Refgene ACTG1

RefSeq NM_001614.3

Base change c.914T>C

AA Change p.M305T

SIFT .

PP2 P

LRT D

Mut Taster D

Mut Assessor ExAC_all H .

ExAC_eas .

17

79478042

79478042

G

C

ACTG1

NM_001614.3

c.895C>G

p.L299V

.

P

D

D

M

.

.

1

1661

4739

0

4690

> 8.5

> 1.0

0.9 - 81.5

17

79478939

79478939

T

A

ACTG1

NM_001614.3

c.353A>T

p.K118M

.

B

D

A

H

.

AD_Pathogenic

3

0

1661

4740

0

4690

> 8.5

> 1.0

0.9 - 81.5

10

73330641

73330641

C

T

CDH23

NM_022124.5

c.719C>T

p.P240L

D

D

D

A

L

0.00009

0.0013 AR_Pathogenic

13

91

1651

4649

24

6938

2.3

5.7

1.2 - 4.5

10

73464800

73464800

G

A

CDH23

NM_022124.5

c.2866G>A

p.E956K

.

D

D

D

M

0.00003

0 AR_Pathogenic

2

15

1662

4725

2

4728

2.8

7.5

0.4 - 20.2

1.7 - 32.8

10

73492049

73492049

G

A

CDH23

NM_022124.5

c.4021G>A

p.D1341N

.

D

D

A

H

> 4.0

NA

10

73498294

73498294

C

T

CDH23

NM_022124.5

c.4249C>T

p.R1417W

.

D

N

D

M

10

73498391

73498391

G

A

CDH23

NM_022124.5

c.4346G>A

p.G1449D

.

D

D

D

M

10

73538025

73538025

A

C

CDH23

NM_022124.5

c.5147A>C

p.Q1716P

.

D

D

D

M

10

73550924

73550924

C

T

CDH23

NM_022124.5

c.6085C>T

p.R2029W

.

D

D

D

H

10

73553004

73553004

C

T

CDH23

NM_022124.5

c.6319C>T

p.R2107X

.

.

D

A

.

.

10

73558125

73558125

A

-

CDH23

NM_022124.5

c.6844delA

p.N2282fs

.

.

.

.

.

.

10

73558958

73558958

G

A

CDH23

NM_022124.5

c.7145G>A

p.R2382Q

D

D

D

D

L

10

73559336

73559336

G

A

CDH23

NM_022124.5

c.7312G>A

p.E2438K

T

B

D

D

N

.

16

21270106

21270106

T

G

CRYM

NM_001888.4

c.941A>C

p.K314T

D

P

D

A

N

.

14

76964643

76964643

C

T

ESRRB

NM_004452.3

c.1144C>T

p.R382C

T

D

D

D

L

8

72211384

72211384

T

C

EYA1

NM_172060.3

c.625A>G

p.S209G

T

B

D

D

M

8

72211437

72211437

C

A

EYA1

NM_172060.3

c.572G>T

p.G191V

D

P

D

D

8

72233984

72233984

C

T

EYA1

NM_172060.3

c.304G>A

p.G102S

T

D

D

13

20763138

20763138

T

C

GJB2

NM_004004.5

c.583A>G

p.M195V

D

D

13

20763209

20763209

-

CGTT

GJB2

NM_004004.5

c.511_512insAACG

p.A171fs

.

.

13

20763294

20763294

G

A

GJB2

NM_004004.5

c.427C>T

p.R143W

D

13

20763313

20763313

G

T

GJB2

NM_004004.5

c.408C>A

p.Y136X

13

20763353

20763353

G

T

GJB2

NM_004004.5

c.368C>A

13

20763421

20763422

AT

-

GJB2

NM_004004.5

c.299_300del

13

20763464

20763464

G

C

GJB2

NM_004004.5

13

20763486

20763486

G

-

GJB2

13

20763530

20763545

CACACGTT CTTGCAGC

13

20763587

20763587

C

13

20763612

20763612

13

20763698

1

.

0.00001 0.00009 0.00003 .

. 0.00003 . .

JPN_C JPN_C AD vs. AR vs. AD vs. CNT AD alt AR alt AD ref AR ref NT alt NT ref CNT OR CNT OR OR _95% CI Pathogenicity AD_Pathogenic 2 1 1662 4739 0 4690 > 5.6 > 1.0 0.5 - 62.3 AD_Pathogenic

3

AR vs. CNT OR_95% CI 0.1 - 15.8

AD vs. CNT p value 0.116

AR vs. CNT p value 0.996

0.1 - 15.8

0.024

NA

0.024

NA

3.6 - 8.9

0.025

0.000

0.601

0.996

0.004

0.4 - 35.5

0 AR_Pathogenic

0

4

1664

4736

0

4690

0.0

NA

0.136

0.0013 AR_Pathogenic

1

9

1663

4731

11

6309

0.3

1.1

0.0 - 2.7

0.5 - 2.6

0.476

0.974

0.0004 AR_Pathogenic

1

11

1663

4729

12

6936

0.3

1.3

0.0 - 2.7

0.6 - 3.0

0.477

0.618

AR_Pathogenic

0

4

1664

4736

0

4690

0.0

> 4.0

NA

0.4 - 35.5

NA

0.136

0.0002 AR_Pathogenic

9

31

1655

4709

13

6869

2.9

3.5

1.2 - 6.7

1.8 - 6.7

0.023

0.000

AR_Pathogenic

0

4

1664

4736

0

4690

0.0

> 4.0

NA

0.4 - 35.5

NA

0.136

AR_Pathogenic

1

3

1663

4737

0

666

> 0.4

> 0.4

0.0 - 6.4

0.0 - 4.1

0.635

0.819

0.0003 AR_Pathogenic

1

5

1663

4735

4

6162

0.9

1.6

0.1 - 8.3

0.4 - 6.1

0.632

0.692

.

AR_Pathogenic

4

3

1660

4737

0

4690

> 11.3

> 3.0

1.3 -101.2

0.3 - 28.6

0.005

0.252

.

AD_Pathogenic

0

2

1664

4738

1

4763

0.0

2.0

NA

0.2 - 22.2

0.582

0.997

0.00070

0.0097 AR_Pathogenic

13

25

1651

4715

44

6852

1.2

0.8

0.7 - 2.3

0.5 - 1.4

0.634

0.522

0.00002

0.0002 AD_Pathogenic

1

3

371

827

51

6439

0.3

0.5

0.0 - 2.5

0.1 - 1.5

0.417

0.259

N

0.00010

0.0018 AD_Pathogenic

2

3

370

827

62

6486

0.6

0.4

0.1 - 2.3

0.1 - 1.2

0.601

0.133

D

N

0.00007

0.0008 AD_Pathogenic

3

2

369

828

21

5775

2.2

0.7

0.7 - 7.5

0.2 - 2.8

0.366

0.810

D

D

M

0.00003

0.0002 AD_Pathogenic

1

6

1663

4734

1

5547

3.3

7.0

0.2 - 53.5

0.8 - 58.4

0.948

0.084

.

.

.

0.00002

0.0002 AR_Pathogenic

0

14

1664

4726

0

666

0.0

> 2.0

NA

0.3 - 15.0

NA

0.319

D

D

A

M

0.00020

0.0002 AR_Pathogenic

9

72

1655

4668

7

5599

4.3

12.3

1.6 - 11.7

5.7 - 26.8

0.004

0.000

.

.

D

D

.

AR_Pathogenic

11

106

1653

4634

16

7026

2.9

10.0

1.4 - 6.3

5.9 - 17.0

0.009

0.000

p.T123N

T

B

N

N

N

0.00050

0.0073 AR_Pathogenic

8

19

1656

4721

46

6986

0.7

0.6

0.3 - 1.6

0.4 - 1.0

0.525

0.091

p.H100fs

.

.

.

.

.

0.00004

0.0006 AR_Pathogenic

2

47

1662

4693

2

1522

0.9

7.6

0.1 - 6.5

1.8 - 31.4

0.680

0.002

c.257C>G

p.T86R

D

D

D

D

M

AR_Pathogenic

6

21

1658

4719

4

6289

5.7

7.0

1.6 - 20.2

2.4- 20.4

0.008

0.000

NM_004004.5

c.235delC

p.L79fs

.

.

.

.

.

0.00040

0.005 AR_Pathogenic

26

452

1638

4288

27

2123

1.2

8.3

0.7 - 2.1

5.6 - 12.3

0.507

0.000

GJB2

NM_004004.5

c.176_191del

p.G59fs

.

.

.

.

.

0.00002

0.0002 AR_Pathogenic

5

58

1659

4682

0

666

> 2.0

> 8.3

0.2 - 17.2

1.1 - 59.7

0.357

0.008

T

GJB2

NM_004004.5

c.134G>A

p.G45E

D

D

D

A

M

AR_Pathogenic

11

106

1653

4634

16

7018

2.9

10.0

1.4 - 6.3

5.9 - 17.0

0.009

0.000

C

T

GJB2

NM_004004.5

c.109G>A

p.V37I

T

D

D

A

M

0.00660

0.0724 AR_Pathogenic

27

101

1637

4639

67

6891

1.7

2.2

1.1 -2.7

1.6 - 3.1

0.028

0.000

20763698

G

A

GJB2

NM_004004.5

c.23C>T

p.T8M

D

P

D

N

L

0.00007

0 AR_Pathogenic

1

1

1663

4739

10

6166

0.4

0.1

0.0 - 2.9

0.0 - 1.0

0.538

0.046

35250822

35250822

G

T

GJB3

NM_024009.2

c.459G>T

p.W153C

D

D

D

D

M

AD_Pathogenic

3

8

1661

4732

2

5496

5.0

4.6

0.8 - 29.7

1.0 - 21.9

0.156

0.069

13

20796930

20796930

-

T

GJB6

NM_006783.4

c.689dupA

p.N230fs

.

.

.

.

.

0 AR_Pathogenic

4

5

1660

4735

0

666

> 1.6

> 0.7

0.2 -14.4

0.1 - 6.0

0.476

0.875

13

20797319

20797319

C

T

GJB6

NM_006783.4

c.301G>A

p.E101K

T

B

D

D

N

0.0001 AR_Pathogenic

0

2

1664

4738

1

4761

0.0

2.0

NA

0.2 - 22.2

0.582

0.997

1

41249975

41249975

C

-

KCNQ4

NM_004700.3

c.210delC

p.G70fs

.

.

.

.

.

AD_Pathogenic

25

0

1639

4740

0

666

> 10.2

0.0

1.4 - 75.1

NA

0.003

NA

1

41284190

41284190

C

G

KCNQ4

NM_004700.3

c.546C>G

p.F182L

T

B

N

A

N

0.00030

0.0045 AD_Pathogenic

3

16

1661

4724

32

5928

0.3

0.6

0.1 - 1.1

0.3 - 1.1

0.090

0.165

1

41304121

41304121

G

A

KCNQ4

NM_004700.3

c.2014G>A

p.V672M

D

D

N

D

N

0.00006

0.0008 AD_Pathogenic

0

3

1664

4737

3

4707

0.0

1.0

NA

0.2 - 4.9

0.710

0.689

18

44109190

44109190

G

A

LOXHD1

NM_144612.6

c.4480C>T

p.R1494X

.

.

D

A

.

0 AR_Pathogenic

0

3

1664

4737

1

4745

0.0

3.0

NA

0.3 - 28.9

0.583

0.616

11

71817106

71817106

C

T

LRTOMT

NM_001145310.3 c.88C>T

p.R30X

.

.

.

A

.

AR_Pathogenic

0

4

1664

4736

0

4690

0.0

> 4.0

NA

0.4 - 35.5

NA

0.136

5

68728503

68728503

G

A

MARVELD2

NM_001244734.1 c.1295+1G>A

.

.

.

D

.

0.00002

0 AR_Pathogenic

0

3

1664

4737

0

4690

0.0

> 3.0

NA

0.3 - 28.6

NA

0.252

5

68736316

68736316

A

-

MARVELD2

NM_001244734.1 c.1507delA

p.K503fs

.

.

.

.

.

0.00003

0.0004 AR_Pathogenic

0

4

1664

4736

8

658

0.0

0.1

NA

0.0 - 0.2

0.000

0.000

5

68737445

68737445

T

A

MARVELD2

NM_001244734.1 c.1605T>A

p.D535E

T

D

D

D

M

0.00001 .

AR_Pathogenic

1

4

1663

4736

6

5612

0.6

0.8

0.1 - 4.7

0.2 - 2.8

0.929

0.961

19

50792843

50792843

G

A

MYH14

NM_001077186.1 c.4804G>A

p.E1602K

D

D

.

D

M

0.00010

0.0019 AD_Pathogenic

3

22

1661

4718

19

6363

0.6

1.6

0.2 - 2.0

0.8 - 2.9

0.580

0.203

22

36698709

36698709

G

A

MYH9

NM_002473.5

c.2404C>T

p.R802W

D

D

D

D

M

0.00007

0.0005 AD_Pathogenic

1

6

1663

4734

2

5264

1.6

3.3

0.1 - 17.5

0.7 - 16.5

0.766

0.226

22

36702021

36702021

C

T

MYH9

NM_002473.5

c.2114G>A

p.R705H

D

D

D

A

H

AD_Pathogenic

4

0

1660

4740

0

4690 > 11.3

0.0

1.3 - 101.2

NA

0.005

NA

17

18022785

18022785

A

G

MYO15A

NM_016239.3

c.671A>G

p.Y224C

D

D

.

N

L

0.0004 AR_Pathogenic

6

16

1658

4724

31

6885

0.8

0.8

0.3 - 1.9

0.4 - 1.4

0.778

0.437

17

18042234

18042234

G

T

MYO15A

NM_016239.3

c.5117G>T

p.G1706V

D

D

.

D

M

AR_Pathogenic

0

2

1664

4738

1

4707

0.0

2.0

NA

0.2 - 21.9

0.587

0.995

17

18046936

18046936

G

A

MYO15A

NM_016239.3

c.5964+3G>A

.

.

.

.

.

AR_Pathogenic

0

2

1664

4738

0

4690

0.0

> 2.0

NA

0.2 - 21.8

NA

0.484

17

18064657

18064657

T

A

MYO15A

NM_016239.3

c.9413T>A

p.L3138Q

D

D

.

D

H

.

AR_Pathogenic

2

3

1662

4737

0

4690

> 5.6

> 3.0

0.5 - 62.3

0.3 - 28.6

0.116

0.252

17

18075505

18075507

CTT

-

MYO15A

NM_016239.3

c.10251_10253del

p.3417_3418del .

.

.

.

.

.

AR_Pathogenic

0

4

1664

4736

3

667

0.0

0.2

NA

0.0 - 0.8

0.036

0.061

17

18036540

18036540

G

T

MYO15A

NM_016239.3

c.4322G>T

p.G1441V

D

D

.

D

M

0.00001

0.0001 AR_Pathogenic

1

5

1663

4735

3

4637

0.9

1.6

0.1 - 8.9

0.4 - 6.8

0.614

0.746

10

26315356

26315356

A

C

MYO3A

NM_017433.4

c.848A>C

p.Q283P

T

P

D

D

M

0.00007

0.0009 AR_Pathogenic

4

14

1660

4726

13

4879

0.9

1.1

0.3 - 2.8

0.5 - 2.4

0.918

0.935

6

76623836

76623836

C

T

MYO6

NM_004999.3

c.3496C>T

p.R1166X

.

.

D

A

.

.

AD_Pathogenic

4

2

1660

4738

0

4690

> 11.3

> 2.0

1.3 - 101.2

0.2 - 21.8

0.005

0.484

11

76853753

76853753

A

G

MYO7A

NM_000260.3

c.19-2A>G

.

.

.

D

.

.

11

76867967

76867967

G

A

MYO7A

NM_000260.3

c.652G>A

D

D

D

D

M

11

76883793

76883793

G

-

MYO7A

NM_000260.3

c.1798-1G>-

.

.

.

.

.

11

76885889

76885889

C

T

MYO7A

NM_000260.3

c.2023C>T

p.R675C

D

D

D

D

H

11

76886438

76886438

C

A

MYO7A

NM_000260.3

c.2115C>A

p.C705X

.

.

D

A

.

11

76890119

76890119

G

T

MYO7A

NM_000260.3

c.2311G>T

p.A771S

D

P

D

D

M

11

76912561

76912561

G

A

MYO7A

NM_000260.3

c.4921G>A

p.E1641K

T

D

D

D

M

11

76916643

76916643

C

T

MYO7A

NM_000260.3

c.5617C>T

p.R1873W

D

D

D

D

M

2

26683865

26683865

C

T

OTOF

NM_194248.2

c.5567G>A

p.R1856Q

D

D

D

D

M

2

26705431

26705431

A

T

OTOF

NM_194248.2

c.1422T>A

p.Y474X

.

.

D

A

.

2

26707353

26707353

A

T

OTOF

NM_194248.2

c.1194T>A

p.D398E

T

B

D

D

L

10

55617017

55617017

C

T

PCDH15

NM_001142763.1 c.3739G>A

p.V1247M

D

D

.

D

10

56138562

56138562

C

T

PCDH15

NM_001142763.1 c.313G>A

p.G105R

D

D

.

7

107303801

107303801

C

G

SLC26A4

NM_000441.1

c.225C>G

p.L75L

.

.

7

107312645

107312645

C

T

SLC26A4

NM_000441.1

c.367C>T

p.P123S

D

7

107314632

107314632

A

G

SLC26A4

NM_000441.1

c.439A>G

p.M147V

7

107314794

107314794

G

T

SLC26A4

NM_000441.1

c.600+1G>T

7

107315389

107315389

G

A

SLC26A4

NM_000441.1

c.601-1G>A

7

107315546

107315546

A

G

SLC26A4

NM_000441.1

c.757A>G

7

107323898

107323898

A

G

SLC26A4

NM_000441.1

7

107323983

107323983

G

A

SLC26A4

NM_000441.1

7

107329611

107329611

C

T

SLC26A4

NM_000441.1

c.1115C>T

7

107330593

107330593

A

T

SLC26A4

NM_000441.1

7

107330645

107330645

G

A

SLC26A4

7

107330648

107330648

C

T

SLC26A4

7

107334899

107334899

G

A

7

107336429

107336429

G

7

107338521

107338521

7

107340560

107340560

7

107340625

7

0.00002

.

.

.

.

.

.

.

. 0.00030 0.00010

.

.

0.00060 .

.

.

. 0.00003

.

. 0.00004 . . .

.

AR_Pathogenic

2

3

1662

4737

0

4690

> 5.6

> 3.0

0.5 - 62.3

0.3 - 28.6

0.116

0.252

0 AD_Pathogenic

1

1

1663

4739

0

4690

> 2.8

> 1.0

0.2 - 45.1

0.1 - 15.8

0.588

0.996

AR_Pathogenic

3

4

1661

4736

0

666

> 1.2

> 0.6

0.1 - 11.6

0.1 -5.0

0.648

0.991

0.0002 AR_Pathogenic

5

4

1659

4736

1

5289

15.9

4.5

1.9 - 136.5

0.5 - 40.0

0.003

0.308

0.0002 AR_Pathogenic

0

4

1664

4736

2

5550

0.0

2.3

NA

0.4 - 12.8

0.948

0.546

AR_Pathogenic

3

9

1661

4731

17

6311

0.7

0.7

0.2 - 2.3

0.3 - 1.6

0.714

0.517

0.00004

0.0002 AR_Pathogenic

0

4

1664

4736

4

5478

0.0

1.2

NA

0.3 - 4.6

0.610

0.882

0.00001

0 AR_Pathogenic

0

2

1664

4738

0

4690

0.0

> 2.0

NA

0.2 - 21.8

NA

0.484

0.0001 AR_Pathogenic

0

4

1664

4736

0

4690

0.0

> 4.0

NA

0.4 - 35.5

NA

0.136

AR_Pathogenic

0

8

1664

4732

0

4690

0.0

> 7.9

NA

1.0 - 63.4

NA

0.014

0.00020

0.0029 AR_Pathogenic

4

16

1660

4724

23

6875

0.7

1.0

0.2 - 2.1

0.5 - 1.9

0.716

0.900

M

0.00040

0.0054 AR_Pathogenic

7

9

1657

4731

8

6164

3.3

1.5

1.2 - 9.0

0.6 - 3.8

0.036

0.585

D

L

0.00010

0 AR_Pathogenic

4

6

1660

4734

9

5609

1.5

0.8

0.5 - 4.9

0.3 - 2.2

0.726

0.850

.

.

.

0.00030

0.0012 AR_Pathogenic

1

5

1663

4735

6

5690

0.6

1.0

0.1 - 4.7

0.3 - 3.3

0.940

0.764

D

D

D

M

AR_Pathogenic

0

3

1664

4737

1

5547

0.0

3.5

NA

0.4 - 33.8

0.523

0.510

D

D

D

D

M

0.00001

0.0001 AR_Pathogenic

1

4

1663

4736

2

5362

1.6

2.3

0.1 - 17.8

0.4 - 12.4

0.775

0.575

.

.

.

D

.

0.00001

0 AR_Pathogenic

0

7

1664

4733

0

4690

0.0

> 6.9

NA

0.9 - 56.4

NA

0.024

.

.

.

D

.

AR_Pathogenic

0

4

1664

4736

4

5608

0.0

1.2

NA

0.3 - 4.7

0.621

0.908

T

P

D

D

L

0.00007

0.0007 AR_Pathogenic

1

5

1663

4735

4

5432

0.8

1.4

0.1 - 7.3

0.4 - 5.3

0.729

0.837

c.919-2A>G

.

.

.

D

.

0.00030

0.0043 AR_Pathogenic

0

27

1664

4713

3

5505

0.0

10.5

NA

3.2 - 34.7

0.789

0.000

c.1001+1G>A

.

.

.

A

.

0.00020

0 AR_Pathogenic

1

2

1663

4738

1

4763

2.9

2.0

0.2 - 45.8

0.2 - 22.2

0.977

0.997

p.A372V

D

D

D

A

M

AR_Pathogenic

0

8

1664

4732

0

4690

0.0

> 7.9

NA

1.0 - 63.4

NA

0.014

c.1174A>T

p.N392Y

D

D

D

D

M

0.00001

0.0001 AR_Pathogenic

0

7

1664

4733

1

4763

0.0

7.0

NA

0.9 - 57.3

0.582

0.076

NM_000441.1

c.1226G>A

p.R409H

D

D

D

D

M

0.00010

0 AR_Pathogenic

0

3

1664

4737

0

4690

0.0

> 3.0

NA

0.3 - 28.6

NA

0.252

NM_000441.1

c.1229C>T

p.T410M

D

D

D

D

M

0.00020

0 AR_Pathogenic

0

26

1664

4714

3

5501

0.0

10.1

NA

3.1 - 33.4

0.788

0.000

SLC26A4

NM_000441.1

c.1315G>A

p.G439R

D

D

N

D

M

0.00002

0 AR_Pathogenic

0

4

1664

4736

2

4688

0.0

2.0

NA

0.4 - 10.8

0.970

0.693

A

SLC26A4

NM_000441.1

c.1489G>A

p.G497S

D

D

D

A

M

0.00002

0.0001 AR_Pathogenic

1

2

1663

4738

0

4690

> 2.8

> 2.0

0.2 - 45.1

0.2 - 21.8

0.588

0.484

A

C

SLC26A4

NM_000441.1

c.1579A>C

p.T527P

D

D

D

D

M

.

.

AR_Pathogenic

0

6

1664

4734

1

5435

0.0

6.9

NA

0.8 - 57.2

0.531

0.090

-

T

SLC26A4

NM_000441.1

c.1648dupT

p.R549fs

.

.

.

.

.

.

.

AR_Pathogenic

1

6

1663

4734

2

2122

0.6

1.3

0.1 - 7.0

0.3 - 6.7

0.832

0.985

107340625

G

A

SLC26A4

NM_000441.1

c.1707+5G>A

.

.

.

.

.

0.00003

0.0002 AR_Pathogenic

0

11

1664

4729

0

4690

0.0

> 10.9

NA

1.4 - 84.5

NA

0.003

107342443

107342443

G

C

SLC26A4

NM_000441.1

c.1975G>C

p.V659L

D

P

D

D

L

0.00001

0.0001 AR_Pathogenic

0

6

1664

4734

0

4690

0.0

> 5.9

NA

0.7 - 49.4

NA

0.042

7

107344815

107344815

T

C

SLC26A4

NM_000441.1

c.2074T>C

p.F692L

T

P

D

D

N

.

.

AR_Pathogenic

1

5

1663

4735

1

5435

3.3

5.7

0.2 - 52.3

0.7 - 49.1

0.958

0.163

7

107350514

107350514

-

GCTGG

SLC26A4

NM_000441.1

c.2105_2106insGCTGG p.K702fs

.

.

.

.

.

.

.

AR_Pathogenic

0

4

1664

4736

0

666

0.0

> 0.6

NA

0.1 - 5.0

NA

0.991

7

107350571

107350571

C

T

SLC26A4

NM_000441.1

c.2162C>T

p.T721M

D

D

D

A

M

0.00006

0 AR_Pathogenic

1

8

1663

4732

0

4690

> 2.8

> 7.9

0.2 - 45.1

1.0 - 63.4

0.588

0.014

7

107350577

107350577

A

G

SLC26A4

NM_000441.1

c.2168A>G

p.H723R

D

D

D

A

M

0.00010

0.0017 AR_Pathogenic

9

125

1655

4615

16

6952

2.4

11.8

1.0 - 5.4

7.0 - 19.8

0.062

0.000

7

107323796

107323796

-

G

SLC26A4

NM_000441.1

c.916dupG

p.I305fs

.

.

.

.

.

0.00002

0.0002 AR_Pathogenic

0

3

1664

4737

2

2122

0.0

0.7

NA

0.1 - 4.0

0.590

0.964

7

107323901

107323901

C

T

SLC26A4

NM_000441.1

c.920C>T

p.T307M

D

D

D

D

L

0.00006

0 AR_Pathogenic

0

4

1664

4736

3

5617

0.0

1.6

NA

0.4 - 7.1

0.799

0.821

15

43893673

43893673

C

T

STRC

NM_153700.2

c.4622G>A

p.R1541Q

T

P

N

D

.

0.00020

0.0027 AR_Pathogenic

3

4

1565

4514

7

5457

1.5

0.7

0.4 - 5.8

0.2 - 2.4

0.837

0.772

11

121023682

121023682

C

T

TECTA

NM_005422.2

c.4198C>T

p.H1400Y

T

D

D

D

N

0.00020

0.0027 AD_Pathogenic

0

3

1664

4737

11

5463

0.0

0.3

NA

0.1 - 1.1

0.141

0.108

11

121038844

121038844

C

T

TECTA

NM_005422.2

c.5668C>T

p.R1890C

D

D

D

A

L

AD_Pathogenic

2

1

1662

4739

0

4690

> 5.6

> 1.0

0.5 - 62.3

0.1 - 15.8

0.116

0.996

9

71869279

71869279

A

G

TJP2

NM_004817.3

c.3562A>G

p.T1188A

D

D

D

D

L

0.00009

0.0013 AD_Pathogenic

8

36

1608

4588

48

6890

0.7

1.1

0.3 - 1.5

0.7 - 1.7

0.476

0.670

21

43796685

43796685

C

T

TMPRSS3

NM_032404.2

c.778G>A

p.A260T

D

D

D

D

L

0.00003

0.0001 AR_Pathogenic

0

7

1664

4733

1

4633

0.0

6.9

NA

0.8 - 55.5

0.593

0.082

21

43809080

43809080

C

T

TMPRSS3

NM_032405.1

c.280G>A

p.G94R

D

D

D

D

M

0.00010

0.0002 AR_Pathogenic

11

30

1653

4710

50

6960

0.9

0.9

0.5 - 1.8

0.6 - 1.4

0.947

0.685

22

38106473

38106473

G

A

TRIOBP

NM_001039141.2 c.154G>A

p.D52N

D

D

.

N

L

0.0016 AR_Pathogenic

4

11

1660

4729

13

6093

1.1

1.1

0.4 - 3.5

0.5 - 2.4

0.934

0.996

22

38167667

38167667

G

A

TRIOBP

NM_007032.5

c.1721G>A

p.R574H

D

D

.

D

M

AR_Pathogenic

2

4

1662

4736

5

4619

1.1

0.8

0.2 - 5.7

0.2 - 2.9

0.763

0.970

11

17553006

17553006

C

T

USH1C

NM_005709.3

c.188G>A

p.R63Q

D

D

D

D

L

0 AR_Pathogenic

4

1

1660

4739

0

4690

> 11.3

> 1.0

1.3 - 101.2

0.1 - 15.8

0.005

0.996

1

215844430

215844430

A

G

USH2A

NM_206933.2

c.14017T>C

p.Y4673H

T

P

U

D

M

AR_Pathogenic

4

14

1518

4344

18

5422

0.8

1.0

0.3 -2.3

0.5 - 2.0

0.873

0.924

1

216051224

216051224

T

C

USH2A

NM_206933.2

c.8559-2A>G

.

.

.

D

.

0.00002

0.0003 AR_Pathogenic

4

5

1518

4353

0

4512

> 11.9

> 5.2

1.3 - 106.5

0.6 - 44.4

0.004

0.067

1

216138779

216138779

T

C

USH2A

NM_206933.2

c.7000A>G

p.N2334D

T

P

N

N

L

0.00009

0.0013 AR_Pathogenic

3

1

1519

4357

2

5178

5.1

0.6

0.9 - 30.6

0.1 - 6.6

0.145

0.881

1

216246607

216246607

G

A

USH2A

NM_206933.2

c.5608C>T

p.R1870W

D

D

N

D

M

0.00040

0.0049 AR_Pathogenic

2

7

1520

4351

22

6164

0.4

0.5

0.1 - 1.6

0.2 - 1.1

0.250

0.090

1

216348605

216348605

G

A

USH2A

NM_206933.2

c.4616C>T

p.T1539I

D

D

U

D

M

0.00008

0.0011 AR_Pathogenic

0

3

1522

4355

4

6174

0.0

1.1

NA

0.2 - 4.8

0.715

0.761

1

216371668

216371668

G

A

USH2A

NM_206933.2

c.4070C>T

p.T1357M

D

D

U

D

M

0.00020

0.0013 AR_Pathogenic

7

26

1515

4332

46

6820

0.7

0.9

0.3 - 1.5

0.5 - 1.4

0.449

0.724

1

216462716

216462716

C

T

USH2A

NM_206933.2

c.1877G>A

p.R626Q

D

D

N

D

M

0.00006

0.0005 AR_Pathogenic

0

3

1522

4355

0

4512

0.0

> 3.1

NA

0.3 - 29.9

NA

0.236

1

216465679

216465679

G

C

USH2A

NM_206933.2

c.1678C>G

p.P560A

T

P

U

D

M

0.00006

0.0007 AR_Pathogenic

0

3

1522

4355

3

4583

0.0

1.1

NA

0.2 - 5.2

0.741

0.729

1

216500979

216500979

C

T

USH2A

NM_206933.2

c.802G>A

p.G268R

D

D

U

D

M

0.00001

0 AR_Pathogenic

2

1

1520

4357

0

4512

> 5.9

> 1.0

0.5 - 62.3

0.1 - 16.6

0.105

0.986

4

6303573

6303573

C

T

WFS1

NM_006005.3

c.2051C>T

p.A684V

D

D

D

D

M

.

.

AD_Pathogenic

1

5

1663

4735

0

4690

> 2.8

> 5.0

0.2 - 45.1

0.6 - 42.4

0.588

0.075

4

6303641

6303641

G

T

WFS1

NM_006005.3

c.2119G>T

p.V707F

D

D

D

D

M

.

.

AD_Pathogenic

2

0

1662

4740

0

4690

> 5.6

0.0

0.5 -62.3

NA

0.116

NA

4

6303644

6303644

C

T

WFS1

NM_006005.3

c.2122C>T

p.R708C

D

D

D

D

M

0.00010

0.0002 AR_Pathogenic

0

4

1664

4736

6

5602

0.0

0.8

NA

0.2 - 2.8

0.396

0.959

4

6303668

6303668

G

A

WFS1

NM_006005.3

c.2146G>A

p.A716T

T

D

D

A

M

0.00001

0 AD_Pathogenic

3

0

1661

4740

0

4690

> 8.5

0.0

0.9 - 81.5

NA

0.024

NA

4

6303707

6303707

G

A

WFS1

NM_006005.3

c.2185G>A

p.D729N

T

B

D

D

L

0 AD_Pathogenic

1

1

1663

4739

2

4738

1.4

0.5

0.1 - 15.7

0.0 - 5.5

0.713

1.000

4

6304029

6304029

A

C

WFS1

NM_006005.3

c.2507A>C

p.K836T

T

D

D

D

L

.

.

AD_Pathogenic

6

1

1658

4739

0

4690

> 17.0

> 1.0

2.0 - 141.1

0.1 - 15.8

0.000

0.996

4

6304030

6304030

G

C

WFS1

NM_006005.3

c.2508G>C

p.K836N

T

D

D

D

L

.

.

AD_Pathogenic

3

0

1661

4740

0

4690

> 8.5

0.0

0.9 - 81.5

NA

0.024

NA

p.D218N

p.I253V

. 0.00003

.

. 0.00003 0.00002

.

.

0.00001 .

.

.

.

.

.

.

.

.

.

0.00020 .

. 0.00001

.

.

0.00010

4 6304112 6304112 G A WFS1 NM_006005.3 c.2590G>A p.E864K D D D A L . . AD_Pathogenic 4 0 1660 4740 0 4690 > 11.3 0.0 1.3 - 101.2 NA 0.005 NA Abbreviations: PP2: PolyPhen2, ExAC_all: Minor allele frequencies in the Exome Aggregation Consortium database, ExAC_eas: Minor allele frequencies in the East Asian population in the Exome Aggregation Consortium database, AD vs. CNT OR: Odds ratio of autosomal dominant or mitochondrial cases compared with JPN_CNT.AR vs. CNT OR: Odds ratio of autosomal recessive or sporadic cases compared with JPN_CNT. JPN_CNT alt: Total alternative allele number in Japanese control population including 2KJPN, HGVD, in house control. JPN_CNT ref: Total reference allele number in Japanese control population including 2KJPN, HGVD, in house control. * Position was on the human genome version GRCh37/hg19.

Supp. Table S2. Minor allele frequency and in silico prediction results of the variants described in the manuscript.

Supplemental Table S2. Minor allele frequency and in silico prediction results of the variants described in the manuscript. Case 1 Chr chr11 chr11

Start End Ref 76867714 76867714 C 76893039

76893039 G

Alt G

Variant MYO7A:NM_000260.3:exon6:c.C479G:p.S160C

1000G ALL .

1000G AFR .

1000G AMR .

1000G EAS .

1000G EUR .

1000G SAS .

ExAC Freq .

ExAC AFR .

ExAC AMR .

ExAC EAS .

ExAC FIN .

ExAC NFE .

ExAC OTH .

ExAC SAS .

ESP6500 ESP6500 ESP6500 SIFT SIFT si_ALL si_AA si_EA score pred . . . 0 D

T

MYO7A:NM_000260.3:exon24:c.G2947T:p.D983Y

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

Alt G

1000G ALL Variant CDH23:NM_022124.5:exon34:c.4463A>G:p.E1488G .

1000G AFR .

1000G AMR .

1000G EAS .

1000G EUR .

1000G SAS .

ExAC Freq .

ExAC AFR .

ExAC AMR .

ExAC EAS .

ExAC FIN .

ExAC NFE .

ExAC OTH .

ExAC SAS .

ESP6500 ESP6500 ESP6500 SIFT si_ALL si_AA si_EA score . . . .

A

CDH23:NM_022124.5:exon51:c.7463G>A:p.R2488H .

.

.

.

.

0.06 T

PP2 score

PP2 pred 1 D

LRT score

0.523 P

LRT pred 0 D 0 D

MutTast er score 1

MutTast MutAss MutAss er essor essor pred score pred final conclusion D 4.61 H Likely Pathogenic

1 D

2.495 M

Uncertain significance

Case 2 Chr chr10 chr10

Start End Ref 73499504 73499504 A 73560493

73560493 G

0.001

0.003

0.0014 .

0.0002

0.0019

0.0004

0.0001

0 6.10E-05

0

0

0.0008

0.0025

SIFT pred .

0.024 D

PP2 score

PP2 pred 1 D

0.976 D

LRT score

LRT pred 0 D 0 D

MutTast er score 1

MutTast MutAss MutAss er essor essor pred score pred final conclusion D 4.21 H Likely Pathogenic

1 D

1.52 L

Likely Pathogenic