SCN5A Variant Y1977N

Summary of observed carriers, functional annotations, and structural context for SCN5A Y1977N. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

65%

4/12 effective observations

Estimated BrS1 penetrance

10%

1/12 effective observations

Total carriers

0 BrS1 · 2 LQT3 · 0 unaffected

Y1977N has not been reported in gnomAD. This residue resides in a Non_Hotspot region for Brugada syndrome and a Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 1 individuals for Brugada syndrome and 2 individuals for LQT3.

In silico predictors

Variant-level computational predictors.
PROVEAN	PolyPhen-2	BLAST-PSSM	REVEL	Penetrance Density BrS (%)	Penetrance Density LQT3 (%)
-8.22	0.949	-0.69	0.843	0	60

PROVEAN scores below -2 suggest deleterious impact. REVEL scores above 0.5–0.75 are often interpreted as likely pathogenic. PolyPhen-2 scores above 0.85 are typically pathogenic. Penetrance density summarises neighbouring residue risk (Kroncke et al. 2019).

Reported carrier data

Observed carriers by publication or cohort.
Source	Year	Carriers	Unaffected	LQT3	BrS1	Other	Other Disease
25904541	2015	1		1	0	0
19716085	2009	1		1	0	0
Literature, cohort, and gnomAD	–	2	0	2	0		–
Variant features alone	–	15	12	2	1	–	–

Totals may differ from individual publications due to duplicate patients removed during curation.

Functional data

Peak and late/persistent current values are relative to wild-type (100% indicates no change). V_1/2 activation and inactivation denote the membrane potentials (mV) at which half-maximal current is achieved.

Published electrophysiology measurements.
PubMed ID	Year	Cell Type	Peak Current (% WT)	V_1/2 Activation (mV)	V_1/2 Inactivation (mV)	Late/Persistent Current (% WT)
25904541	2015
19716085	2009

Nearby variants

Neighbouring residues within 15 Ångström provide structural context. Variants listed in the right-most column have been observed clinically or in gnomAD.

Previously observed variants near Y1977N.
Neighbour residue	Distance (Å)	Observed variants
1962	15	P1962L, P1962S,
1963	14	P1963L,
1964	14	S1964F,
1965	13	S1965G, S1965N,
1966	13
1967	12	p.S1967LfsX12,
1968	11	I1968T, I1968S, I1968N, I1968V, I1968M,
1969	11
1970	10	p.S1970_S1972del,
1971	9
1972	8
1973	8	F1973L,
1974	7
1975	5	P1975T,
1976	4	S1976C,
1977	0	Y1977N,
1978	4
1979	5
1980	7	V1980F,
1981	8
1982	8	R1982T,
1983	9	A1983V, A1983G,
1984	10	T1984I,
1985	11	S1985R,
1986	11	D1986N, D1986G,
1987	12	N1987K,
1988	13	L1988R,
1989	13
1990	14	V1990L,
1991	14	R1991Q, R1991W,
1992	15	G1992A,