Table 1: Outlining truth sets for cliPE experiments.

For most cliPE experiments, the following truth sets are critical to validate the MAVE. For some genes which lack a portion of the truth set, such as PTEN or CHEK2 which have a limited number of BLB variants listed in ClinVar, it is important to consider how the data analysis portion of the workflow may be impacted.

	Assay validation truth set	Clinical truth set
Negative control	Synonymous and missense variants present in general population database such as gnomAD	Missense variants classified as benign or likely benign in ClinVar
Positive control	Premature truncation variants in the targeted regions of the gene	Missense variants classified as pathogenic or likely pathogenic in ClinVar