TABLE 1.

Summary of the types of uncertainties associated with prenatal WES, and their definitions

Type of uncertainty	Subtype	Definition
1) Uncertainty related to clinical effectiveness	Diagnostic yield	Likelihood to provide a diagnosis.
2) Uncertainties related to incomplete knowledge	Gene‐disease correlations	Phenotype associated with a variant is unknown (prenatally and postnatally), including its variability in expression and the natural history.
	How a genetic anomaly presents prenatally	New phenotypes associated with genes that have limited natural history information in the prenatal period. Or postnatal phenotype associated with pathogenic variant (e.g. mental disability) is not or only partially recognized prenatally.
	Pathogenicity and variants of unknown significance (VUS)	Insufficient evidence to classify variants as (likely) benign or (likely) pathogenic.
3) Uncertainties unrelated to the primary clinical question	Secondary findings	Pathogenic variant(s) not related to indication of testing, but intentionally searched for as an additional analysis next to the standard test.
	Incidental findings	Pathogenic variant(s) not related to indication of testing and are identified inadvertently (unexpected result).
4) Uncertainties related to the technology	Technical validity of a result	False positives, false negatives, insufficient depth of read.
	Possible incomplete result	For example, One autosomal recessive variant compatible with the fetal phenotype, but no second variant is identified.
5) Uncertainties related to the condition	Incomplete penetrance	Chance that a pathogenic variant presents with symptoms. Not everyone with the same genetic predisposition will be affected (reduced or incomplete penetrance).
	Variable expression variants	A pathogenic variant with 100% penetrance where patients with the same variant can show different symptoms (variable expression).