Table 3:

CLIA approved sequencing options

	Sanger sequencing	Whole exome “slice” or panel	Whole exome sequencing
Strengths	• High accuracy • Can include splice junctions • Often reflexes to deletion/duplication testing	• Affordable • Often more timely than WES • No off target findings	• Most comprehensive
Weaknesses	• Limited number of genes sequenced (i.e. best used from his pre-test probability) • Some genes are incompletely sequenced and only “hot spots” are sequenced	• Same weaknesses as WES for technical approach although coverage is typically higher	• Usually takes the longest to run and analyze • Some exons are missed • Not sensitive (at this time) for deletions and duplications • Regulatory (non-coding) mutations missed • Off target findings common
Insurance coverage/cost	• The easiest of the three • Cost is highly variable but single genes are typically less than WES	• Mid-range difficulty • Less expensive than WES	• Most difficult • Most expensive generally
Notes		• Panel content highly variable • Some panels use WES data and targeted analysis, others use specific gene capture which leads to higher coverage	• Bioinformatic analysis variable • Strength of variant association can be difficult to discern