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Table 1 Definite pathogenic and highly suspected variants in LDS genes detected in our cohort

From: Genetic profiling and cardiovascular phenotypic spectrum in a Chinese cohort of Loeys-Dietz syndrome patients

Patient ID

Gene

Transcript

Nucleotide change

Amino acid change

MAF

in ExAC

MAF in gnomAD

Domain

Source

Pathogenicity

Evidence

Note

AD1413

TGFBR1

NM_004612

c.614 T > C

p.Ile205Thr

.

.

Pkinase_Tyr

Maternal

LP

PM2, PP3, PS2$

 

AD623–1

TGFBR1

NM_004612

c.644G > C

p.Arg215Pro

.

.

 

De novo

LP

PS2, PM2, PP3

 

AD808

TGFBR1

NM_004612

c.664G > A

p.Gly222Arg

.

0.0000289

Pkinase_Tyr

 

LP

PM2, PP1_Strong, PP3

 

AD264

TGFBR1

NM_004612

c.683_685del

p.228del

.

.

 

De novo

LP

PS2, PM2, PS4_Supporting, PM4

a

AD692–1

TGFBR1

NM_004612

c.702_704del

p.235del

.

.

 

De novo

LP

PS2, PM2, PM4

 

AD453

TGFBR1

NM_004612

c.722C > T

p.Ser241Leu

.

.

 

NA

LP

PM2, PS4_Supporting, PS2

 

AD371

TGFBR1

NM_004612

c.934G > A

p.Gly312Ser

0.00000942

0.00000398

 

NA

LP

PP3, PM2, PS4_Supporting, PP1_Strong

a

AD641–1

TGFBR1

NM_004612

c.997G > A

p.Asp333Asn

.

.

 

De novo

LP

PS2, PM2, PP3

 

AD78

TGFBR1

NM_004612

c.1459C > T

p.Arg487Trp

.

.

 

NA

P

PS4, PM2, PM5, PP1_Strong, PP3

a

AD703–1

TGFBR1

NM_004612

c.1459C > T

p.Arg487Trp

.

.

 

Maternal

P

PS4, PM2, PM5, PP1_Strong, PP3

 

AD1346

TGFBR1

NM_004612

c.1459C > T

p.Arg487Trp

.

.

 

NA

P

PS4, PM2, PM5, PP1_Strong, PP3

 

AD1362

TGFBR1

NM_004612

c.1460G > A

p.Arg487Gln

.

.

 

Paternal

P

PS2, PS3_Supporting, PS4_Moderate, PM2, PP3

 

AD1804

TGFBR2

NM_003242

c.95-2A > G

 

0.0000293

0.0006

 

Paternal

LP

PVS1, PM2

 

AD257

TGFBR2

NM_003242

c.1067G > C

p.Arg356Pro

.

.

Pkinase_Tyr

Paternal

(Mosaic)

P

PS2_Very Strong, PS4_Moderate, PM2, PP3

ab

AD22

TGFBR2

NM_003242

c.1139 T > G

p.Leu380Arg

.

.

 

De novo

LP

PS2, PM2, PP3

a

AD888

TGFBR2

NM_003242

c.1275G > C

p.Met425Ile

.

.

Pkinase_Tyr

De novo

LP

PS2, PM2, PP3

 

AD1181

TGFBR2

NM_003242

c.1363 T > C

p.Trp455Arg

.

.

Pkinase_Tyr

 

VUSLP

PM2, PP3

Assumed de novo in AD1181’s mother

AD536

TGFBR2

NM_003242

c.1449dupT

p.Cys483fs

.

.

Pkinase_Tyr

NA

LP

PVS1, PM2

 

AD617–1

TGFBR2

NM_003242

1517delA

p.Asn506fs

.

.

Pkinase_Tyr

NA

P

PVS1, PM2, PP1

 

AD1784

TGFBR2

NM_003242

c.1525-1G > C

 

.

.

 

NA

LP

PVS1, PM2

 

AD153

TGFBR2

NM_003242

c.1538 T > C

p.Val513Ala

.

.

Pkinase_Tyr

De novo

LP

PS2, PM2

a

AD682–1

TGFBR2

NM_003242

c.1582C > T

p.Arg528Cys

.

.

 

De novo

P

PS2, PP3, PM2, PS4_Moderate, PS3_Supporting, PM5

 

AD497

TGFBR2

NM_003242

c.1609C > T

p.Arg537Cys

.

.

 

NA

P

PS2, PS3_Moderate, PS4_Moderate, PM2,PP3, PP1_Strong

a

AD1550

SMAD3

NM_005902

c.233_234insGG

p.Ser78fs

.

.

 

NA

LP

PVS1, PM2

 

AD1736

SMAD3

NM_005902

c.365_366insGAATCCCTACCAC

p.Val122fs

.

.

 

Paternal

LP

PVS1, PM2

 

AD1061

SMAD3

NM_005902

c.1041delG

p.Glu347fs

.

.

 

NA

LP

PVS1, PM2

 

AD792

SMAD3

NM_005902

c.1118G > A

p.Arg373His

.

.

  

VUSLP

PM2, PP3, PS3_Supporting, PS4_Supporting

 

AD1297

SMAD3

NM_005902

c.1247C > T

p.Ser416Phe

.

.

 

De novo

LP

PS2, PM2, PP3

 

AD535

SMAD2

NM_005901

c.593dupA

p.His198fs

.

.

 

De novo

LP

PS2, PM2

 

AD802

TGFB2

NM_003238

c.905G > A

p.Arg302His

.

.

TGF_beta

Paternal

VUSLP

PM2, PM5, PP3

 

AD1065

TGFB3

NM_003239

c.605_623del

p.Phe202fs

.

.

 

Maternal

LP

PVS1, PM2

 

AD631–1

TGFB3

NM_003239

c.646 + 2 T > G

 

.

.

 

Paternal

LP

PVS1, PM2

 
  1. Note: NA not available; MAF in ExAC was the maximal allele frequency from the public version (20160423), and MAF in gnomAD was the maximal allele frequency from gnomAD v2.1.1; P, pathogenic; LP, likely pathogenic; VUS, variant of uncertain significance; a, reported in our previous article [11]; bThis variant was previously classified as VUS, and then upgraded into pathogenic after the father was confirmed to carry a mosaic mutation in the same site; $ This variant was confirmed to be de novo in patient AD1413’s mother