SCN5A Variant Y403D

Summary of observed carriers, functional annotations, and structural context for SCN5A Y403D. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

32%

1/10 effective observations

Estimated BrS1 penetrance

13%

1/10 effective observations

Total carriers

0 BrS1 · 0 LQT3 · 0 unaffected

Y403D 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 1 individuals for LQT3.

In silico predictors

Variant-level computational predictors.
PROVEAN	PolyPhen-2	BLAST-PSSM	REVEL	Penetrance Density BrS (%)	Penetrance Density LQT3 (%)
NA	NA	NA	0.986	9	41

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
Literature, cohort, and gnomAD	–	0	0	0	0		–
Variant features alone	–	15	13	1	1	–	–

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

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 Y403D.
Neighbour residue	Distance (Å)	Observed variants
403	0
1659	13
1643	14	I1643L,
404	6	L404Q, L404V,
1773	14
1765	13
396	10	V396L, V396A,
1653	8
254	14
1771	7	I1771T,
401	7	S401P,
1652	12	M1652R, M1652T,
1634	14	L1634P,
1764	11	V1764F, c.5290delG,
371	13	Q371E,
409	12	L409V, L409P,
928	15	L928P,
1650	6	L1650F,
260	10
366	15
1656	11
365	15
369	10	M369K,
1767	7	Y1767C,
1660	11	I1660S, I1660V,
1654	8
1648	13
1769	11
402	6	F402L, F402L, F402L,
1766	14	M1766V, M1766L, M1766L, M1766T,
1649	10	A1649V,
1768	9	I1768V,
1774	12	N1774D, c.5321_5324dupACTT,
256	11
399	6
397	9	I397F, I397T, I397V,
405	8
1657	7
261	13
1709	15	p.T1709del, T1709R, T1709M,
1772	11	L1772V,
1645	15	T1645M,
395	11
394	12
410	12	A410V,
1770	10	I1770V,
1658	10
264	13
1651	11
259	14
408	11
253	12
407	8
1763	14	V1763L, V1763L, V1763M,
263	14	V263I,
1775	12	p.F1775LfsX15, F1775V,
370	13	T370M,
1661	12	G1661R, G1661R, G1661E,
1655	11
406	7	N406K, N406S, N406K,
368	13
411	14	V411M,
398	7
1647	10
257	11
400	5	G400A, G400E, G400R, G400R,
1646	11
1664	14