Table 1.
Previously described and novel SMAD3 gene mutations
| Exon | c‐Notation | p‐Notation | Domain | Reference | Times reported | Effect |
|---|---|---|---|---|---|---|
| 1 | c.2T > C | p.Met1Thr | MH1 | Haller et al. (2015) | 1 | Pathogenic |
| 1 | c.3G > A | p.Met1Ile | MH1 | Fitzgerald et al. (2014) | 1 | Pathogenic |
| 2 | c.221G > A | p.Arg74Gln | MH1 | Current study | 2 | Likely pathogenic |
| 2 | c.266G > A | p.Cys89Tyr | MH1 | Zhang et al. (2015) | 1 | Pathogenic |
| 2 | c.269G > A | p.Arg90His | MH1 | Current study | 1 | Likely pathogenic |
| 2 | c.281G > T | p.Trp94Leu | MH1 | Blinc et al. (2015) | 1 | VUS |
| 2 | c.290T > G | p.Leu97Arg | MH1 | Current study | 1 | VUS |
| 2 | c.300_301insAGGGCCGGCAGGC | p.His101Argfs*14 | MH1 | Current study | 1 | Pathogenic |
| 2 | c.313delG | p.Ala105Profs*11 | MH1 | van de Laar et al. (2012) | 1 | Pathogenic |
| 2 | c.335C > T | p.Ala112Val | MH1 | (Regalado et al., 2011) | 1 | Likely pathogenic |
| 2 | c.370C > A | p.Pro124Thr | MH1 | (Garcia‐Bermudez et al., 2017) | 1 | VUS |
| 2 | c.374A > G | p.Tyr125Cys | MH1 | Current study | 1 | Likely pathogenic |
| 2 | c. 374A > C | p.Tyr125Ser | MH1 | Current study | 1 | Likely pathogenic |
| 3 | c.401‐6G > A | p.Val134Aspfs*33 | MH1 | ( Campens et al., 2015 ), Current study | 2 | Pathogenic |
| 3 | c.401_405dup | p.Pro136Phefs*52 | MH1 | (Berthet et al., 2015) | 1 | Pathogenic |
| 3 | c.455delC | p.Pro152Hisfs*34 | Linker | ( Courtois et al., 2017 ) | 1 | Pathogenic |
| 3 | c.511G > T | p.Glu171* | Linker | Current study | 1 | Pathogenic |
| 3 | c.532+1G > C | Linker | Current study | 1 | Pathogenic | |
| 4 | c.539_540insC | p.Pro180Thrfs*7 | Linker | (van de Laar et al., 2012), Current study | 2 | Pathogenic |
| 4 | c.546delT | p.Gly183Alafs*3 | Linker | (Campens et al., 2015) | 1 | Pathogenic |
| 4 | c.584_585insTC | p.Gln195Hisfs*3 | Linker | (Campens et al., 2015) | 1 | Pathogenic |
| 5 | c.652delA | p.Asn218Thrfs*23 | Linker | (Regalado et al., 2011) | 1 | Pathogenic |
| 6 | c.668delC | p.Pro223Glnfs*18 | Linker | (Aubart et al., 2014) | 1 | Pathogenic |
| 6 | c.715G > A | p.Glu239Lys | MH2 | (Regalado et al., 2011), (Campens et al., 2015) | 4 | Pathogeic |
| 6 | c.728G > C | p.Arg243Pro | MH2 | Current study | 1 | Likely pathogenic |
| 6 | c.733G > A | p.Gly245Arg | MH2 | (Aubart et al., 2014) | 1 | Likely pathogenic |
| 6 | c.741_742delAT | p.Thr247Profs*61 | MH2 | (van de Laar et al., 2011) | 1 | Pathogenic |
| 6 | c.742T > C | p.Phe248Leu | MH2 | (Aubart et al., 2014) | 1 | Likely pathogenic |
| 6 | c.748G > A | p.Ala250Thr | MH2 | Current study | 1 | Likely pathogenic |
| 6 | c.762delC | p.Met255* | MH2 | Current study | 1 | Pathogenic |
| 6 | c.772G > C | p.Asp258His | MH2 | Current study | 1 | Likely pathogenic |
| 6 | c.782C > T | p.Thr261Ile | MH2 | (van de Laar et al., 2011) | 1 | Pathogenic |
| 6 | c.788C > T | p.Pro263Leu | MH2 | (van de Laar et al., 2012) | 1 | VUS |
| 6 | c.797C > A | p.Ser266* | MH2 | (Haller et al., 2015) | 1 | Pathogenic |
| 6 | c.803G > T | p.Arg268Leu | MH2 | ( Schubert et al., 2016 ), Current study | 2 | Likely pathogenic |
| 6 | c.836G > A | p.Arg279Lys | MH2 | (Regalado et al., 2011) | 2 | Likely pathogenic |
| 6 | c.859C > T | p.Arg287Trp | MH2 | (van de Laar et al., 2011), (Campens et al., 2015) | 2 | Likely pathogenic |
| 6 | c.860G > A | p.Arg287Gln | MH2 | ( Aubart et al., 2014 ), Current study | 2 | Likely pathogenic |
| 6 | c.861delG | p.Arg288Aspfs*53 | MH2 | Current study | 1 | Pathogenic |
| 7 | c.862_871+1dupAGACACATCGG | p.Arg292Aspfs*53 | MH2 | (Aubart et al., 2014) | 1 | Pathogenic |
| 7 | c.887T > C | p.Leu296Pro | MH2 | (Campens et al., 2015) | 1 | Likely pathogenic |
| 7 | c.988A > G | p.Thr330Ala | MH2 | (Ye et al., 2013) | 1 | Likely pathogenic |
| 7 | c.1009+1G > A | MH2 | Current study | 1 | Pathogenic | |
| 7 | c.1009+2T > A | MH2 | (Nevidomskyte et al., 2017) | 1 | Pathogenic | |
| 8 | c.1045G > C | p.Ala349Pro | MH2 | (van de Laar et al., 2012) | 1 | Likely pathogenic |
| 8 | c.1080dupT | p.Glu361* | MH2 | Current study | 1 | Pathogenic |
| 8 | c.1081G > T | p.Glu361* | MH2 | (van de Laar et al., 2012) | 1 | Pathogenic |
| 8 | c.1091A > G | p.Tyr364Cys | MH2 | Current study | 1 | Likely pathogenic |
| 8 | c.1102C > T | p.Arg368* | MH2 | ( Aubart et al., 2014 ), Current study | 2 | Pathogenic |
| 8 | c.1141G > C | p.Gly381Arg | MH2 | Current study | 1 | Likely pathogenic |
| 9 | c.1155‐2A > G | MH2 | (Campens et al., 2015) | 1 | Pathogenic | |
| 9 | c.1170_1179del | p.Ser391Alafs*7 | MH2 | (Wischmeijer et al., 2013) | 1 | Pathogenic |
| 9 | c.1179_1180dupC | p.Cys394Leufs*4 | MH2 | (Aubart et al., 2014) | 1 | Pathogenic |
| 9 | c.1185G > C | p.Trp395Cys | MH2 | Current study | 1 | VUS |
| 9 | c.1199T > C | p.Leu400Pro | MH2 | Current study | 1 | VUS |
| 9 | c.1208C > T | p.Pro403Leu | MH2 | (Martens et al., 2013) | 1 | Likely pathogenic |
| 9 | c.1222G > C | p.Asp408His | MH2 | Current study | 1 | Likely pathogenic |
| 9 | c.1224C > A | p.Asp408Glu | MH2 | Current study | 1 | Likely pathogenic |
| 9 | c.1243G > C | p.Gly415Arg | MH2 | Current study | 1 | Likely pathogenic |
| 9 | c.1247C > T | p.Ser416Phe | MH2 | Current study | 1 | Likely pathogenic |
| 9 | c.1259G > A | p.Arg420His | MH2 | (Proost et al., 2015) | 1 | VUS |
| 9 | c.1265C > T | p.Ser422Phe | MH2 | Current study | 1 | Likely pathogenic |
| 9 | c.1267A > G | p.Ser423Gly | MH2 | (Aubart et al., 2014) | 1 | Likely pathogenic |
| 9 | c.1268G > A | p.Ser423Asn | MH2 | Current study | 1 | Likely pathogenic |
| 9 | c.1274C > T | p.Ser425Phe | MH2 | Current study | 1 | VUS |
| Deletion from exon 2 onwards: Chr2.hg19: g.(67,408,242)_(67,603,013)del | (Hilhorst‐Hofstee et al., 2013) | 1 | Pathogenic | |||
| Deletion 15q22.33 | Current study | 1 | Pathogenic | |||
Mutations identified in this study are indicated in bold.