Table 3. Genome sequencing tests.

Genetic tests	Method	Types and technical differences	Advantages	Disadvantages
Multigene panels	- Sequences groups of genes causing a phenotype	- Sequence analysis with/without deletion/duplication analysis	- May be able to detect mutations that are missed in comprehensive gene testing (for example, ARX gene and SCN1A 23) - Can design specific multigene panels - Generates fewer variants of unknown significance	- Tests only for the genes in the panel unless done as part of whole exome sequencing
Comprehensive gene testing
Exome sequencing	- Sequences protein coding regions only	- Sequence enrichment - Single- or paired-end sequencing - Read depth - Accuracy of base calling - Family testing-trio sequencing	- More useful for hard-to-characterize epilepsy phenotypes - Sequencing has reported sensitivity. - Covers genes that may not be in multigene panels - Can identify variants of uncertain significance that may be pathogenic - Can be reanalyzed	- Generates a large number of variants of unknown significance - Cannot detect imprinting errors, uniparental heterodisomy, nucleotide repeats, pseudogenes, non-coding regions, mitochondrial genes, mosaic changes, large copy number variation, or chromosome rearrangements - Results may take four or more weeks to return.
Genome sequencing	- Sequences all coding and non-coding regions	- Has similar laboratory limitations as listed for exome sequencing	- Has the same advantages as exome sequencing - Less arduous sample preparation - Can identify structural variants and chromosome breakpoints in non-coding regions	- Many of the same limitations as exome sequencing - Some exons may not be sequenced - More expensive than exome sequencing
Chromosome microarray	- Detects copy number deletions or duplications of variable sizes	- Oligonucleotide array (comparative genomic hybridization) - Polymorphism genotypic (single- nucleotide polymorphism)	- Available in many medical facilities - Covered by insurance and Medicaid	- Does not analyze all exomes or genome - Does not sequence genes in the targeted regions analyzed

This table lists currently available sequencing methods and their advantages and disadvantages. All of these tests are commercially available and we review the yield of these tests in studies of pediatric patients with epilepsy. The information in the table is from Wallace and Bean ²⁴ and Helbig et al. ²³.