Table 1.

SCN5A variants identified in children with arrhythmogenic syndromes.

Variant	Variant Type	dbSNP	gnomAD Global MAF	Domain Location	Site	Functional Interpretation *	Reference
p.Arg34fs * 60	Frameshift	-	0	N-Terminus	-	LOF	[27]
p.Val240Met	Missense	rs199473076	1.4 × 10−5	DI	Cytoplasmic S4-S5	GOF	[22]
p.Arg811Cys	Missense	rs794728864	0	DII	S4	-	-
p.Arg893His	Missense	rs199473172	4.0 × 10−6	DII	Pore	LOF	[25]
p.Arg1195His	Missense	rs199473596	2.5 × 10−5	Interdomain DII-DIII	Cytoplasmic	LOF/GOF	[27]
p.Asp1275Asn	Missense	rs137854618	8.0 × 10−6	DIII	S3	LOF	[24]
p.Trp1345_Ser1349delinsPhe	Inframe del/ins		0	DIII	S5	-	-
p.Arg1632Cys	Missense	rs878855292	4.0 × 10−6	DIV	S4	LOF/GOF	[28]
p.Arg1644His	Missense	rs199473282	4.0 × 10−6	DIV	Cytoplasmic S4-S5	GOF	[26]
p.Gly1661Arg	Missense	rs199473292	0	DIV	S5	LOF	[23]
p.Thr1708Asn	Missense	-	0	DIV	Pore	LOF/GOF	[25]
p.Ser1710Leu	Missense	rs137854604	1.6 × 10−5	DIV	Pore	LOF/GOF	[21]
p.Pro1730Leu	Missense	rs1060501142	8 × 10−6	DIV	Extracellular pore	-	-
p.Asp1741Glyfs * 48	Frameshift	rs1251085820	0	DIV S5/S6	-	-	-
p.Ala1778Asp	Missense	-	0	C-Terminus	Cytoplasmic	-	-
p.Leu1821fs * 10	Frameshift	rs794728924	0	C-Terminus	Cytoplasmic	LOF/GOF	[29]

* Functional interpretation according to functional studies expressing the variants in different heterologous systems. MAF: minor allele frequency; LOF: loss of function; GOF: gain of function.