Table 2.

Selected genome editing assays for testing human variant at scale

Method	Paper	Description	Assay
SGE	(40)	HDR-mediated integration of variants at Cas9-targeted loci	Hexamer effects on splicing in HEK293 (n = 4048); DBR1 variant fitness in HAP1 (n = 365)
	(69)	(as above)	BRCA1 variant effects on HAP1 fitness (n = 3893) and transcript levels (n = 2646)
	(110)	Cloning-free SGE with single-stranded DNA repair templates	CARD11 variant effects on TMD8 growth +/− ibrutinib and transcript levels (n = 2542)
Base editor screens	(119)	gRNA libraries used with base editing to introduce specific variants	n = 745 gRNAs targeting all exons of BRCA1 for fitness effects in HAP1
	(117)	(as above)	n = 70 000+ gRNAs tested in various cell lines (HAP1, MELJUSO, A375 and HT29) and assays (drug sensitivity, resistance and fitness of 57 000+ ClinVar variants)
	(118)	(as above)	n = 50 000+ gRNAs to tile 86 DNA damage response genes, assaying essentiality and response to DNA damage drugs in MCF10A, MCF7 and HAP1
Saturation prime editing	(121)	Prime editing gRNAs designed to achieve saturation mutagenesis	Variant effects on lysosome trafficking (NPC1; n = 256) and growth (BRCA2; n = 465) in 293T