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Table 3 Pathogenic and likely pathogenic mutations adhered to ACMG guidelines in 172 refractory epilepsy children

From: Novel and de novo mutations in pediatric refractory epilepsy

Case code

Gene

Gene location

Transcript

cDNA change

Protein change

SIFT

PP2

MT

HSF

GERP++

MAF-ExAC

MAF-KG

Parental Origin

ACMG scoring

ACMG pathogenicity

Diagosis

13

SCN1A

chr2–166,901,702

NM_006920

c.1513A > T

p.K505X

–

–

A

–

6.17 (C)

–

–

De novo

PVS1 + PS2 + PM2

LP

DS

23

SCN1A

chr2–166,854,657 166,854,660 a [101]

NM_006920

c.4331_4334del

p.E1444fs

–

–

–

–

–

–

–

De novo

PVS1 + PS1 + PS2 + PM2

P

DS

26

SCN1A

chr2–166,870,270

NM_001165963

c.3689T>C

p.L1230P

D

D

D

–

5.28 (C)

–

–

De novo

PS2 + PM1 + PM2 + PP3

LP

DS

35

SCN1A

chr2–166,900,287 166,900,288

NM_001165963

c.1934_1935del

p.V645fs

–

–

–

–

–

–

–

De novo

PVS1 + PS2 + PM2

P

DS

38

SCN1A

chr2–166,859,121

NM_006920

c.G4112T

p.G1371V

D

P

D

–

5.54 (C)

–

–

De novo

PS2 + PM2

LP

DS

53

SCN1A

chr2–166,894,306 166,894,337

NM_001165963

c.2895_2926del

p.Q965fs

–

–

–

–

–

–

–

Unknown

PVS1 + PM2

LP

DS

56

SCN1A

chr2–166,908,355 a [102]

NM_006920

c.838T > C

p.W280R

D

D

D

–

5.41 (C)

–

–

De novo

PS1 + PS2 + PM2 + PP3

P

DS

65

SCN1A

chr2–166,850,927

NM_006920

c.4549-1G > C

splicing

–

–

D

+

5.76 (C)

–

–

De novo

PVS1 + PS2 + PM2

P

DS

115

SCN1A

chr2–166,848,614

NM_006920

c.5138C > A

p.A1713D

D

D

D

–

5.8 (C)

–

–

De novo

PS2 + PM2 + PP3

LP

DS

124

SCN1A

chr2–166,848,438 a [103]

NM_006920

c.5314G > A

p.A1772T

D

D

D

–

5.69 (C)

–

–

De novo

PS1 + PS2 + PM2 + PP3

P

DS

130

SCN1A

chr2–166,854,634 166,854,639 a [101]

NM_006920

c.4352_4356del

p.Y1451Cfs*22

–

–

–

–

–

–

–

De novo

PVS1 + PS1 + PS2 + PM2

P

DS

140

SCN1A

chr2–166,911,210 166,911,211

NM_006920

c.539delT

p.L180X

–

–

–

–

–

–

–

De novo

PVS1 + PS2 + PM2

P

DS

148

SCN1A

chr2–166,901,579

NM_001165963

c.1636G > T

p.E546X

–

–

A

–

6.17 (C)

–

–

Unknown

PVS1 + PM2

LP

DS

149

SCN1A

chr2–166,894,430 a [104]

NM_006920

c.2769G > A

p.M923I

D

D

D

–

5.18 (C)

–

–

Paternal

PS1 + PM2 + PP3

LP

DS

162

SCN1A

chr2–166,848,043 166,848,045

NM_001165963

c.5740_5742del

p.1914_1914del

–

–

–

–

–

–

–

De novo

PS2 + PM2 + PM4

LP

DS

172

SCN1A

chr2–166,903,330

NM_006920

c.1327G > T

p.E443X

–

–

A

–

5.31 (C)

–

–

De novo

PVS1 + PS2 + PM2

P

DS

93

SCN2A

chr2–166,243,416

NM_001040142

c.4712T > C

p.I1571T

D

D

D

–

5.17 (C)

–

–

De novo

PS2 + PM1 + PM2 + PP3

LP

OS

55

KCNQ2

chr20–62,073,781 a [105]

NM_172107

c.794C > T

p.A265V

D

P

D

–

3.38 (C)

–

–

De novo

PS1 + PS2 + PM2

P

OS

90

STXBP1

chr9–130,423,419 a [53]

NM_003165

c.364C > T

p.R122X

–

–

A

–

4.92 (C)

–

–

Unknown

PVS1 + PS1 + PM2

P

OS-WS

52

ADSL

chr22–40,745,935

NM_000026

c.253C > T

p.R85X

–

–

A

–

5.59 (C)

–

–

Maternal

PVS1 + PM2

LP

WS

chr22–40,742,633 [58]

NM_000026

c.71C > T

p.P24L

T

B

D

–

0.153 (N)

–

–

Paternal

PM2

UC

89

KCNT1

chr9–138,651,532 a [106]

NM_020822

c.862G > A

p.G288S

T

D

D

–

5.05 (C)

–

–

De novo

PS1 + PS2 + PM1 + PM2

P

WS

104

CDKL5

chrX-18,593,592 18,593,593

NM_003159

c.265delT

p.F89Lfs*24

–

–

–

–

–

–

–

De novo

PVS1 + PS2 + PM2

P

WS

151

STXBP1

chr9–130,428,529

NM_003165

c.748C > T

p.Q250X

–

–

A

–

5.72 (C)

–

–

De novo

PVS1 + PS2 + PM2

P

WS

29

SYNGAP1

chr6–33,393,659 33,393,662

NM_006772

c.274_277del

p.G92fs

–

–

–

–

–

–

–

De novo

PVS1 + PS2 + PM2

P

Doose

164

SLC2A1

chr1–43,396,517

NM_006516

c.296T > G

p.M99R

D

B

D

–

5.51 (C)

–

–

De novo

PS2 + PM2

LP

GLUT1-DS

30

MECP2

chrX-153,296,516 a [63]

NM_001110792

c.799C > T

p.R267X

–

–

A

–

3.55 (C)

–

–

De novo

PVS1 + PS1 + PS2 + PM2

P

Rett

32

TSC2

chr16–2,126,095 a [91]

NM_000548

c.2666C > T

p.A889V

D

D

D

–

5.09 (C)

–

–

Paternal

PS1 + PM2 + PP3

LP

TSC

94

TSC2

chr16–2,130,180 a [107]

NM_000548

c.3412C > T

p.R1138X

–

–

A

–

4.74 (C)

–

–

De novo

PVS1 + PS1 + PS2 + PM2

P

TSC

TSC2

chr16–2,130,366 a [66]

NM_000548

c.3598C > T

p.R1200W

D

D

D

–

4.74 (C)

–

–

De novo

PS1 + PS2 + PM2 + PP3

P

98

TSC2

chr16–2,138,467

NM_001077183

c.5079C > G

p.Y1693X

–

–

D

–

0.137 (N)

–

–

Paternal

PVS1 + PM2

LP

TSC

TSC2

chr16–2,138,465 2,138,466

NM_001077183

c.5077delT

p.Y1693fs

–

–

–

–

–

–

–

Paternal

PVS1 + PM2

LP

7

SCN8A

chr12–52,184,209 a [108]

NM_001177984

c.4324G > A

p.E1442K

D

D

D

–

4.68 (C)

–

–

Paternal

PS1 + PM2 + PP3

LP

UEE

IQSEC2

chrX-53,263,621 53,263,622

NM_001111125

c.4246_4247insG

p.S1416fs

–

–

–

–

–

–

–

De novo

PVS1 + PS2 + PM2

P

63

CACNA1A

chr19–13,566,019 a [109]

NM_001127221

c.301G > C

p.E101Q

D

D

D

–

5.01 (C)

–

–

De novo

PS1 + PS2 + PM1 + PM2 + PP3

P

UEE

66

SCN8A

chr12–52,200,885 a [110]

NM_001177984

c.5492G > A

p.R1831Q

D

D

D

–

4.91 (C)

–

–

De novo

PS1 + PS2 + PM2 + PP3

P

UEE

69

PCDH19

chrX-99,551,873 99,551,874

NM_001184880

c.2849-1G > −

splicing

–

–

–

+

–

–

–

Unknown

PVS1 + PM2

LP

UEE

157

GABRB3

chr15–26,812,802 a [111]

NM_021912

c.761C > T

p.S254F

D

D

D

–

6.06 (C)

–

–

De novo

PS1 + PS2 + PM1 + PM2 + PP3

P

UEE

160

GABRA1

chr5–161,309,645 a [112]

NM_001127648

c.641G > A

p.R214H

D

D

D

–

5.34 (C)

–

–

De novo

PS1 + PS2 + PM1 + PM2 + PP3

P

UEE

54

CHD2

chr15–93,540,231

NM_001271

c.3640G > T

p.G1214X

–

–

A

–

5.64 (C)

–

–

De novo

PVS1 + PS2 + PM2

P

UEE

40

VRK2

chr2–58,312,086

NM_001130483

c.C256 + 1G > A

splicing

–

–

D

+

5.86 (C)

–

–

Unknown

PVS1 + PM2

LP

UE

44

ATP1A2

chr1–160,098,521

NM_000702

c.1097G > T

p.G366V

D

D

D

–

4.77 (C)

–

–

De novo

PS2 + PM1 + PM2 + PP3

LP

UE

68

TSC1

chr9–135,772,854

NM_000368

c.2768_2769insC

p.L924Ffs*26

–

–

–

–

–

–

–

De novo

PVS1 + PS2 + PM2

P

UE

79

SLC9A6

chrX-135,080,322 135,080,336

NM_001042537

c.582_595del

p.Y194fs

–

–

–

–

–

–

–

De novo

PVS1 + PS2 + PM2

P

UE

  1. Abbreviations: M male, F female, m month, y year, SIFT Sorts intolerant from tolerant (D, damaging; T, tolerant), PP2, polymorphism phenotyping v2 (D, damaging; P, possible damaging; B, benign), MT mutation taster (D, disease causing; A, disease causing automatic), HSF human splicing finder (+, altering splicing), GERP++ genomic evolutionary rate profiling (C, conserved; N, nonconserved), KG 1000 Genomes project, LP likely pathogenic, P pathogenic, DS Dravet syndrome, OS Ohtahara syndrome, OS-WS OS syndrome evolves to West syndrome, WS West syndrome, Doose Doose syndrome, GLUT1-DS glucose transporter type 1 deficiency syndrome, Rett Rett syndrome, TSC tuberous sclerosis complex, UEE unclassified epileptic encephalopathy, UE unclassified refractory epilepsy
  2. a Mutations have been reported in HGMD database