. Author manuscript; available in PMC: 2018 Dec 15.

Published in final edited form as: Genet Med. 2018 Jun 15;21(1):161–172. doi: 10.1038/s41436-018-0044-2

Table 4.

Reasons for Negative ES Results in the 23 Genes that were Determined to be Diagnostic (n=18) or a Candidate Gene (n=5)

Categories Related to a Negative ES	Subcategory	Reasons	Examples in our study (inclusive of diagnoses and candidate genes)
Analytical Approach (35%)	Difficult Regions of Exome	Variants not detected due to capture kit not containing probes resulting in missed data	PLA2G6
	Technical Limitations of ES	Variant calling software limitations (Indels, Structural variants and CNVs)	ANTXR2, NPHP1, MECP2, HDAC8, ITPA
	Variant Filtering/Calling	Stringent filtering, Synonymous variants	TBX2, SON
Knowledge Gap (35%)	None	Novel Candidate Genes with No Known Disease Association	KRT19, CTBS, DROSHA, RNF2, HNRNPK AGTPBP1, NACC1, ASXL2
Variability in Laboratory Reporting (22%)	Variants not Prioritized	Laboratory focused on de novo variants	EFL1
Variability in Laboratory Reporting (22%)	Variant Interpretation	Poor phenotypic fit determination by laboratory	MYBPC1, CACNA1C, HEPACAM, CAD
Unknown Reasons (8%)	None	Reasons not available from pertinent laboratory	CACNA1A, IRF2BPL