Table 2.

Exons Were Categorized as Clinically Significant, Uncertain Significance, Clinically Insignificant, or Noncoding on the Basis of the Pieces of Evidence Listed

Exon designation (in genes with a clinical validity of at least moderate)	Evidence used for designation
Clinically significant exon	• Evidence that exon is required for biological function (eg, literature, absence of high frequency LoF variant in general population)
	AND/OR
	• No alternative splicing
Exon of uncertain significance	• No expression data in the literature
	AND
	• Alternative splicing
	AND/OR
	• 1 High-frequency LoF variant in gnomAD (>0.3%)
Clinically insignificant exon	• Literature confirms exon is not expressed in tissue of clinical relevance
	AND/OR
	• >1 High-quality, high-frequency LoF variant in gnomAD (>0.3%)
Noncoding exon	• Exon does not code for protein

gnomAD, Genome Aggregation Database; LoF, loss of function.