Table 1.

Types of results that can be generated by genome-wide sequencing

Variant type	Clinical example
Primary diagnosis	Detection of sequence-level variant in the NSD1 gene that is diagnostic of Sotos syndrome, in the presence of Marfan-like features (6)
Possible diagnosis	Detection of one sequence level variant in the ZFYVE26 gene in a child with spastic paraplegia. Homozygous or compound heterozygous mutations in this gene are associated with autosomal recessive spastic paraplegia type 15. However, with only one variant detected, the molecular diagnosis cannot be confirmed. Further investigations could identify a second variant (e.g., a deletion) which would confirm a diagnosis (12).
Uninformative test result	Detection of biallelic variants in TRIT1 gene in a child with microcephaly, profound developmental delay, hypotonia, epilepsy, and brain anomalies. This gene has never been reported to be a disease-causing gene in humans. The identification of genotypically and phenotypically similar children combined with more extensive analyses identified that mutations in this gene explain the phenotype among these children (14).
Dual diagnosis	Detection of a variant in the ITPR1 gene responsible for spinocerebellar ataxia type 29 in a 2-year-old female presenting with ataxia, motor, and language delay. Pathogenic mutation was inherited from her father. At age 5 she presented with seizures which had never been reported to be associated with SCA 29. Her mother had a childhood diagnosis of Landau-Kleffner syndrome with seizures. Analysis revealed a de novo pathogenic mutation in the GRIN2A gene in the proband and her mother, known to be associated with Landau- Kleffner syndrome. The family was counseled regarding the 2 separate autosomal dominant diseases that were identified in the proband, each inherited from a different affected parent (21).
Predictive risk result	Detection of sequence-level variant in the KCNH2 gene which is associated with risk for Long QT syndrome. Potential for medical actionability would typically prompt a laboratory to report this variant (22,23).
Pharmacogenomic result	Detection of polymorphisms in cytocrome P450 (CYP) enzymes (CYP2C9, CYP2C19) that can lead to differences in serum concentrations and anti-epileptic drug clearance with a greater risk of concentration-dependent adverse effects (30).