Table 3 Inclusion criteria for genes with various gene–disease evidence levels comparing diagnostic gene panels with exome/genome testing

ClinGen framework^3,^a		Definitive	Strong	Moderate	Limited		No evidence
Gene category		Genes associated with disease			Genes of uncertain significance
Test purpose	Predominant diagnostic approach				Genes with emerging evidence	Genes with no emerging evidence	Genes with no evidence
Confirmation of clinical Dx	Disease-focused multigene panel; other non–sequencing-based ancillary assays	Include	Include	Include^b	Typically exclude^c,d	Exclude	Exclude
Establish genetic diagnosis for clinically complex cases	Exome/genome^e	Include	Include	Include^b	Additional requirements^d

^aGenes with conflicting evidence reported (disputed, refuted) are not appropriate for diagnostic gene panels.
^bIndicate in the report that evidence for the disease association is still building. Variants are unlikely to be classified above likely pathogenic.
^cAlthough broad inclusion of genes of uncertain significance (GUSs) in diagnostic panels is discouraged, there are scenarios where inclusion may be meaningful (see discussion in “Clinical sensitivity”).
^dReport with specific statement that disease association and inheritance has not been established. Results from these genes should be separated from the clinical result to the extent possible within the reporting system.
^eConsent process specific to exome/genome testing required.

Quick links

Search