Table 3

Paralogue annotation of novel variants identified in SCN5A

SCN5A variant
CDS	Protein	Region	Cases (n=2111)	Exon	Paralogue	Paralogue variant	Paralogue disease	Consensus
c.278T>C	p.F93S	N-terminus	1	3	SCN1A	F90S	Myoclonic epilepsy of infancy	5
c.281T>G	p.I94S	N-terminus	1	3	SCN1A	I91T	Myoclonic epilepsy of infancy	5
c.362G>A	p.R121Q	N-terminus	2	3	SCN1A	R118S	Myoclonic epilepsy of infancy	9
c.533C>G	p.A178G	TM domain 1	1	5	SCN1A	A175V	Dravet syndrome	9
					SCN1A	A175T	Myoclonic epilepsy of infancy	9
c.659C>T	p.T220I	TM domain 1	2	6	SCN1A	T217K	Myoclonic epilepsy of infancy	9
c.694G>A	p.V232I	TM domain 1	2	6	CACNA1H	R212R	Autism spectrum disorder	9
c.1100G>T	p.R367L	TM domain 1	1	9	SCN1A	R377Q	Generalised epilepsy with febrile seizures	9
					SCN1A	R377L	Dravet syndrome	9
c.1120T>G	p.W374G	TM domain 1	1	9	SCN1A	W384R	Dravet syndrome	9
					SCN1A	W384X	Myoclonic epilepsy of infancy	9
c.1157G>A	p.G386E	TM domain 1	2	10	SCN1A	G396E	Dravet syndrome	8
c.1156G>A	p.G386R	TM domain 1	1	10	SCN1A	G396E	Dravet syndrome	8
c.1187T>C	p.V396A	TM domain 1	1	10	SCN1A	V406F	Dravet syndrome	9
c.1186G>C	p.V396L	TM domain 1	1	10	SCN1A	V406F	Dravet syndrome	9
c.2047T>G	p.C683G	Interdomain Linker I-II	1	14	SCN9A	C699Y	Dravet syndrome	3
					CACNA1H	R744Q	Childhood absence epilepsy	3
c.2150C>T	p.P717L	TM Domain 2	1	14	SCN1A	P768L	Myoclonic epilepsy of infancy	8
c.2553C>A	p.F851L	TM Domain 2	1	16	SCN1A	F902C	Myoclonic epilepsy of infancy	9
c.2633G>A	p.R878H	TM Domain 2	5	16	SCN1A	R931C	Myoclonic epilepsy of infancy	8
					SCN9A	R896Q	Congenital indifference to pain	8
					SCN1A	R931H	Epilepsy	8
c.2657A>C	p.H886P	TM Domain 2	1	16	SCN1A	H939Q	Myoclonic epilepsy of infancy	9
					SCN1A	H939Y	Dravet syndrome	9
					CACNA1H	W962C	Autism spectrum disorder	9
c.2677C>T	p.R893C	TM Domain 2	2	16	SCN1A	R946S	Generalised epilepsy of infancy	9
					SCN1A	R946C	Myoclonic epilepsy of infancy	9
					SCN1A	R946H	Myoclonic epilepsy of infancy	9
c.2678G>A	p.R893H	TM Domain 2	3	16	SCN1A	R946S	Generalised epilepsy of infancy	9
					SCN1A	R946C	Myoclonic epilepsy of infancy	9
					SCN1A	R946H	Myoclonic epilepsy of infancy	9
c.2701G>A	p.E901K	TM Domain 2	3	16	SCN1A	E954K	Dravet syndrome	9
c.3695G>A	p.R1232Q	TM Domain 3	1	21	SCN1A	R1245Q	Myoclonic epilepsy of infancy	7
c.3758A>G	p.E1253G	TM Domain 3	1	21	SCN1A	E1266A	Dravet syndrome C	9
c.3813G>C	p.W1271C	TM Domain 3	1	21	SCN1A	W1284S	Dravet syndrome	9
c.3968T>G	p.V1323G	TM Domain 3	1	23	SCN9A	V1299F	Paroxysmal extreme pain disorder	9
c.4057G>A	p.V1353M	TM Domain 3	2	23	SCN1A	V1366I	Generalised epilepsy with febrile seizures	9
c.4079T>G	p.F1360C	TM Domain 3	1	23	CACNA1A	F1404C	Episodic ataxia	9
c.4226A>G	p.Y1409C	TM Domain 3	1	23	SCN1A	Y1422C	Myoclonic epilepsy of infancy	9
c.4234C>T	p.L1412F	TM Domain 3	1	23	CACNA1F	L1079P	Night blindness	9
c.4255A>G	p.K1419E	TM Domain 3	1	24	CACNA1C	E1115K	BrS	9
c.4258G>C	p.G1420R	TM Domain 3	1	24	SCN1A	G1433R	Dravet syndrome	9
					SCN1A	G1433E	Myoclonic epilepsy of infancy	9
					SCN1A	G1433V	Dravet syndrome	9
c.4283C>T	p.A1428V	TM Domain 3	1	24	SCN1A	A1441P	Myoclonic epilepsy of infancy	9
c.4321G>C	p.E1441Q	TM Domain 3	1	25	CACNA1A	G1483R	Episodic ataxia	9
					SCN1A	E1454K	Dravet syndrome	9
c.4342A>C	p.I1448L	TM Domain 3	1	25	SCN1A	L1461I	Myoclonic epilepsy of infancy	9
c.4343T>C	p.I1448T	TM Domain 3	1	25	SCN1A	L1461I	Myoclonic epilepsy of infancy	9
c.4346A>G	p.Y1449C	TM Domain 3	1	25	SCN1A	Y1462C	Myoclonic epilepsy of infancy	9
					CACNA1A	F1491S	Episodic ataxia	9
					SCN1A	Y1462H	Dravet syndrome	9
c.4387A>T	p.N1463Y	TM Domain 3	1	25	SCN1A	N1476K	Dravet syndrome	9
c.4402G>T	p.V1468F	TM Domain 3	1	25	SCN4A	V1293I	Paramyotoniacongenita	9
c.4573G>A	p.V1525M	TM Domain 4	1	27	SCN1A	V1538I	Dravet syndrome	9
c.4642G>A	p.E1548K	TM Domain 4	3	27	SCN1A	E1561K	Dravet syndrome	9
c.4747C>T	p.R1583C	TM Domain 4	2	27	SCN1A	R1596C	Cryptogenic focal epilepsy	9
					SCN1A	R1596L	Dravet syndrome	9
					SCN1A	R1596H	Generalised epilepsy with febrile seizures	9
c.4748G>A	p.R1583H	TM Domain 4	1	27	SCN1A	R1596C	Cryptogenic focal epilepsy	9
					SCN1A	R1596L	Dravet syndrome	9
					SCN1A	R1596H	Generalised epilepsy with febrile seizures	9
c.4981G>C	p.G1661R	TM Domain 4	1	28	SCN1A	G1674R	Myoclonic epilepsy of infancy	9
c.4981G>A	p.G1661R	TM Domain 4	2	28	SCN1A	G1674R	Myoclonic epilepsy of infancy	9
c.5015C>A	p.S1672Y	TM Domain 4	2	28	SCN1A	A1685D	Myoclonic epilepsy of infancy	9
					SCN1A	A1685V	Febrile seizures	9
c.5134G>A	p.G1712S	TM Domain 4	1	28	SCN1A	G1725C	Dravet syndrome	9

Forty-five out of 122 novel missense variants identified in 2111 unrelated BrS patients5 were annotated. In addition, 26 of the 70 SCN5A missense variants previously reported to be pathogenic were annotated (see supplementary table S2, available online only).
SCN5A coordinates given with respect to transcripts NM_198056/NP_932173 (Refseq), ENST00000333535/ENSP00000328968 (Ensembl), LRG_289t1/LRG_289p1 (Locus Reference Genomic).
BrS, Brugada syndrome; CDS, coding DNA sequence; TM, transmembrane.