Patient

Gene

Chromosome location

Transcript exon

Nucleotide Amino acid

Homozygous/Heterozygous

Normal human frequency

Prediction

Pathogenicity analysis

Genetic pattern

Disease/Phenotype

Variation source

Case A

1. Genetic variants with highly correlated clinical phenotypes and well-documented pathogenicity

not found

2. Large sample data support susceptible sites

ATP7A

chrX: 7730

1954

NM_ 00005

2; exon23

c.4390A > G

(p.I1464V)

hemi

0.0166

-

-

1. XLR

2. XLR

3. XLR

1. Menkes disease

2. Occipital Angle syndrome

3. X-linked distal spinal muscular atrophy type 3

3. Other mutations with insufficient pathogenic evidence need to be further combined with clinical analysis, and the possibility of pathogenesis cannot be ruled out

GABR

G2

chr5: 1615

24870

NM_ 0008

16; exon4

c.548 + 6C > A

(splicing)

het

5.454E−5

-

Uncertain

1. AD

2. AD

3. AD

1. Generalized epilepsy with febrile convulsion plus type 3

2. Familial febrile epilepsy 8

3. Epileptic encephalopathy in early infancy 74

Mother

Case B

1. Genetic variants with highly correlated clinical phenotypes and well-documented pathogenicity

not found

2. Other mutations with insufficient pathogenic evidence need to be further combined with clinical analysis, and the possibility of pathogenesis cannot be ruled out

SCN9A

chr2: 1670

85398

NM_ 0029

77; exon22

c.3976A > C

(p.I1326L)

het

0.00090

D

Uncertain

1. AD

2. AD

3. AR

4. AD

5. AD

1. Systemic epilepsy with febrile convulsion type 7

2. Primary erythromelalgia

3. Congenital insensitivity to pain

4. Dravet syndrome, repair

5. Paroxysmal pain

Mother

3. Other variation information

MYH11

Chr16: 15818116

NM_ 0024

74; exon31

c.4267A > C

(p.N1423H)

het

-

B

Uncertain

AD

Familial thoracic aortic aneurysm and aortic dissection type 4

CAD

Chr2: 27456870

NM_ 0043

41; exon22

c.3400-6C > T

(splicing)

het

0.00004

-

Uncertain

AR

Congenital glycosylation disease Iz type

ARV1

Chr1: 231131724

NM_ 0227

86; exon4

c.667A > G

(p.I223V)

het

0

B

Uncertain

AR

Early infantile epileptic encephalopathy, type 38

Case C

1. Genetic variants with highly correlated clinical phenotypes and well-documented pathogenicity

not found

2. Other mutations with insufficient pathogenic evidence need to be further combined with clinical analysis, and the possibility of pathogenesis cannot be ruled out

SPTAN1

chr9: 131394

760-

131394760

NM_0011

30438; exon54

c.7010_ 7011ins

TAAG

(p.F2337fs)

het

0.00060

-

Uncertain

AD

Epileptic encephalopathy of early childhood type 5

Father

3. Other variation information

RELN

chr7: 10312

4262

NM_0050

45; exon62

c.10019C > T

(p.S3340L)

het

0

B

Uncertain

1. AR

2. AD

1. Anencephaly

2. Familial temporal lobe epilepsy 7

MTOR

chr1: 11194

424

NM_0049

58; exon37

c.5230C > T

(p.H1744Y)

het

0.00020

B

Uncertain

AD

Smith-Kingsmore

syndrome

Case D

1. Genetic variants with highly correlated clinical phenotypes and well-documented pathogenicity

not found

2. Other variation information

ARHG

EF15

chr17: 82163

54

NM_1737

28; exon3

c.716G > A

(p.R239H)

het

0.0000084

B

Uncertain

-

Epileptic

encephalopathy

MAGI2

chr7: 786365

30-78636531

NM_0123

01; exon2

c.302-9delT

(splicing)

het

0.0039

-

Uncertain

AR

Nephrotic

syndrome

type 15

Case E

Genetic variants with highly correlated clinical phenotypes and well-documented pathogenicity

not found

The specific list of tested genes is shown in the attachment.