Table 1.

Functional classification of residues in long QT proteins.

		Residues with published variants in LQT proteins							Residues with disease variants mapped from paralogues
Protein		LQT	ODP	Benign	PB	Conflict	UN	Total	LQT	ODP	Benign	PB	Conflict	UN	Total
KCNQ1	LQT1	178	8	12	5	15	458	676	36	1	1	0	2	34	74
KCNH2	LQT2	249	4	32	4	14	856	1159	27	0	0	0	0	37	64
SCN5A	LQT3	328	23	34	6	30	1595	2016	95	4	0	1	2	303	405
ANK2	LQT4	9	5	31	18	1	3860	3924	0	0	0	0	0	6	6
KCNE1	LQT5	22	0	5	2	4	96	129	3	0	1	2	0	10	16
KCNE2	LQT6	12	1	2	0	1	107	123	2	0	1	0	1	24	28
KCNJ2	LQT7	33	1	3	1	0	389	427	17	0	0	0	0	78	95
CACNA1C	LQT8	8	0	3	17	0	2110	2138	2	0	0	1	0	586	589
Totals		839	42	122	53	65	9471	10592	182	5	3	4	5	1078	1277
Percentage		7.9%	0.4%	1.2%	0.5%	0.6%	89.4%		14.3%	0.4%	0.2%	0.3%	0.4%	84.4%

Left panel: for each protein, residues are categorised according to the phenotype associated with variants at that residue: variation at the residue causes definite long QT, short QT or Brugada syndrome (LQT); causes other disease phenotype (ODP); is benign (Benign) or is probably benign (PB). A number of residues have conflicting reports of pathogenicity in the literature (Conflict) and many residues have no reported variation and are unannotated (UN). Right panel: residues identified by mapping of disease-causing variants from paralogues are significantly enriched for known disease-causing variants (p=4.8×10⁻⁷, Fisher’s exact test), and annotate 1078 novel putative disease-causing loci.