TABLE II.
Rare Genetic Variants in COL3A1, FBN1, and SMAD3 Identified in Adolescent Idiopathic Scoliosis Cases†
| Gene and Case | Genomic Position | Base Change | Protein Change | Frequency in ExAC Database | Sex | Curve‡ | Height§ | Weight§ | Ghent Systemic Score# | Beighton Score# | Genetics Evaluation and Echocardiogram** | Interpretation | Reference |
| COL3A1 | |||||||||||||
| 6294001 | chr2:189856935 | G > A | R326Q | 1 of 122,932 | F | 69 | 7 | 67 | NA | NA | N | VUS | |
| 6292001 | chr2:189873814 | C > G | N1230K | F | 48 | 38 | 25 | 1 | 1 | N | VUS | ||
| 6388001 | chr2:189876375 | A > G | K1426E | F | 50 | 93 | 96 | 3 | 0 | N | VUS | ||
| FBN1 | |||||||||||||
| 6128001 | chr15:48902952 | T > A | I107L | F | 84 | 20 | 21 | NA | NA | N | VUS | ||
| 6340001 | chr15:48826300 | T > G | N280T | M | 48 | >99 | 99 | 3 | 0 | Y | VUS | ||
| 6377001 | chr15:48795990 | T > G | N703H | F | 50 | 57 | 62 | 1 | 1 | Y | VUS | ||
| 6623001 | chr15:48791223 | G > T | A709E | F | 85 | 93 | >99 | NA | NA | N | VUS | Single report, no details16 | |
| 6623001 | chr15:48791224 | C > T | A709T | F | 85 | 93 | >99 | NA | NA | N | VUS | ||
| 6683001 | chr15:48787732 | T > C | P825A | 1 of 122,446 | F | 90 | 66 | 44 | 3 | 1 | N | VUS | Patient with aortic dilation, skeletal features, and ectopia lentis31, patient with isolated ectopia lentis32 |
| 6556001 | chr15:48779275 | C > T | V1197I | 6 of 122,898 | F | 77 | 38 | 95 | 3 | 3 | N | VUS | |
| 6226001 | chr15:48764870 | A > C | L1405R | 6 of 122,898 | F | 97 | 91 | 85 | 2 | 4 | Y | VUS | Single report, no details16 |
| 6272001 | chr15:48760155 | A > G | M1576T | 10 of 122,930 | F | 90 | 21 | 40 | NA | NA | N | VUS | Two patients with isolated aortic aneurysm17,21 |
| 6418001 | chr15:48760155 | A > G | M1576T | 10 of 122,930 | F | 65 | >99 | 87 | 4 | 1 | Y | VUS | Two patients with isolated aortic aneurysm17,21 |
| 6442001 | chr15:48760155 | A > G | M1576T | 10 of 122,930 | F | 35 | 89 | 89 | 5 | 4 | Y | VUS | Two patients with isolated aortic aneurysm17,21 |
| 6320001 | chr15:48736768 | C > T | G2003R | F | 66 | 7 | 30 | 4 | 0 | N | VUS | ||
| 6111001 | chr15:48725128 | T > A | Y2225F | M | 95 | 93 | 86 | 5 | 2 | Y | VUS | ||
| 6386001 | chr15:48712949 | A > G | I2585T | F | 93 | 98 | 92 | 10 | 2 | Y** | Pathogenic | Patients with Marfan syndrome16-18 | |
| 6674001 | chr15:48073503 | T > C | N2767S | 4 of 122,914 | F | 50 | 42 | 31 | 5 | 2 | N | VUS | Single report, no details16 |
| 6005001 | chr15:48703201 | C > T | 2868I | M | 55 | 91 | 95 | 6 | 9 | Y | VUS | ||
| SMAD3 | |||||||||||||
| 6234001 | chr15:67457343 | T > C | M1T | M | 80 | 75 | 97 | NA | NA | Y | Pathogenic | ||
| 6281001 | chr15:67473717 | C > A | S161* | F | 70 | 97 | 78 | NA | NA | N | Pathogenic |
†
NA = not available and VUS = variant of unknown significance.
‡
The values are given in degrees.
§
The values are given in percentiles.
#
The values are the scores, given in points.
**
The aorta was dilated on an echocardiogram.