Phenotypes, identified gene names, inheritance patterns, causative variants and reasons for initial variant non-detection of the 29 new diagnoses after reanalysis
| New diagnosis after reanalysis | N=29* |
| Phenotypes, n (%) | |
| Developmental delay/intellectual disability | 25 (86.2) |
| Epilepsy | 11 (37.9) |
| Dystonia | 8 (27.6) |
| Neuropathy | 3 (10.3) |
| Failure to thrive/short stature | 2 (6.9) |
| Myopathy | 1 (3.4) |
| Renal tubular acidosis | 1 (3.4) |
| Spastic paraplegia | 1 (3.4) |
| Stroke | 1 (3.4) |
| Visual impairment | 1 (3.4) |
| Gene name (n) | |
| Autosomal recessive disorder | SHQ1 (8), TBC1D24 (2), GLS (1), SLC12A1 (1), SLC25A3 (1), TBCD (1), TTN (1) |
| Autosomal dominant disorder | MNF2 (2), SATB2 (2), BPTF (1), CREBBP (1), FGF12 (1), GRIN2B (1), HCN1 (1), MORC2 (1), RNF213 (1), STXBP1 (1), TRIP12 (1), TUBB4 (1) |
| Mode of inheritance | |
| Autosomal recessive disorder, n (%) | 15 (51.7) |
| Compound heterozygosity | 12 |
| Homozygous mutations | 3 |
| Autosomal dominant disorder, n (%) | 14 (48.3) |
| De novo | 12 |
| Inherited | 2 |
| Causative variants | |
| Single nucleotide variant, n (%) | 26 (89.7) |
| Exonic variant | 24 |
| Deep intronic splicing variant | 2 |
| Structural variation, n (%) | 3 (10.3) |
| Causative variant alleles | N=44 |
| Genetic novelty, n (%) | 29 (65.9) |
| Autosomal recessive disorder | 24 |
| Autosomal dominant disorder | 5 |
| Mutation type, n (%) | |
| Missense | 28 (63.6) |
| Nonsense | 7 (15.9) |
| Duplication | 4 (9.1) |
| Deletion | 3 (6.8) |
| Splicing | 2 (4.5) |
| Reasons for variants not detected in initial WGS | N=29 |
| Variant reclassification, n (%) | 9 (31) |
| Analytical issue, n (%) | 9 (31) |
| New emerging disease–gene association, n (%) | 8 (27.6) |
| Clinical update, n (%) | 3 (10.3) |
*Additional information appears in online supplemental table S1.
WGS, whole-genome sequencing.