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. 2020 Jan 8;15:6. doi: 10.1186/s13023-019-1282-3

Table 1.

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

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

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