Table 1

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 reanalysisN=29*
Phenotypes, n (%)
 Developmental delay/intellectual disability25 (86.2)
 Epilepsy11 (37.9)
 Dystonia8 (27.6)
 Neuropathy3 (10.3)
 Failure to thrive/short stature2 (6.9)
 Myopathy1 (3.4)
 Renal tubular acidosis1 (3.4)
 Spastic paraplegia1 (3.4)
 Stroke1 (3.4)
 Visual impairment1 (3.4)
Gene name (n)
 Autosomal recessive disorderSHQ1 (8), TBC1D24 (2), GLS (1), SLC12A1 (1), SLC25A3 (1), TBCD (1), TTN (1)
 Autosomal dominant disorderMNF2 (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 heterozygosity12
  Homozygous mutations3
 Autosomal dominant disorder, n (%)14 (48.3)
  De novo12
  Inherited2
Causative variants
 Single nucleotide variant, n (%)26 (89.7)
  Exonic variant24
  Deep intronic splicing variant2
 Structural variation, n (%)3 (10.3)
Causative variant allelesN=44
Genetic novelty, n (%)29 (65.9)
 Autosomal recessive disorder24
 Autosomal dominant disorder5
Mutation type, n (%)
 Missense28 (63.6)
 Nonsense7 (15.9)
 Duplication4 (9.1)
 Deletion3 (6.8)
 Splicing2 (4.5)
Reasons for variants not detected in initial WGSN=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.