Table 1.
Overview of likely disease‐causing FBN1 and FBN2 variants in gnomAD
| FBN1 exons 23‐34 | FBN1 all exons | FBN2 exons 23‐34 | FBN2 all exons | |
|---|---|---|---|---|
| Nonsense and frameshift (category I) | 2 | 8 | 5 | 29a (27) |
| Splicing (category II) | 0 | 26 (10) | 0 | 36 (25) |
| In‐frame indels (category III) | 1 | 9 (6) | 0 | 8 (5) |
| Disulfide bonds (category IV) | 1 | 8 | 4 | 36 (31) |
| Calcium binding (category IV) | 4 | 12 (12) | 6 (5) | 49 (23) |
| HGMD 2019.1/ClinVar 2019.5 (category V)b | 1 | 4 (3) | 0 | 0 |
|
Sensu stricto selected sequence variants (categories I‐V) / (Prevalence) |
9:138 632 / (0.65:10 000) |
67:138 632 / (4.83:10 000) |
39:138 632 / (2.81:10 000) |
158:138 632 / (11.40:10 000) |
| Sensu lato selected sequence variants (category VI)c | 566 (40) | 880 (162) | 321 (71) | 1.999 (301) |
| All variants (categories I‐VI) / (Prevalence) |
575:138 632 / (41.48:10 000) |
947:138 632 / (68.31:10 000) |
360:138 632 / (25.97:10 000) |
2,157:138 632 / (155.59:10 000) |
| All individuals in gnomAD (exomes and genomes) | 138 632 | |||
Note: Numbers indicate the total number of variants, while numbers in parenthesis indicate the number of unique variants.
Abbreviations: gnomAD, Genome Aggregation Consortium; HGMD, Human Gene Mutation Database; indel, small insertion/deletion.
Nonsense/frameshift variants were counted regardless of their position in FBN2.
Only sequence variants not already included in categories I‐IV and passing manual evaluation were counted.
Sequence variants predicted as "damaging" or "deleterious" by all of the six used in silico prediction tools (FATHMM, FATHMM‐MKL, MutationAsessor, MutationTaster, PolyPhen2, SIFT) not contained in I‐V were counted; see also Supporting Information Table S1.