SCN5A Variant F402C

Summary of observed carriers, functional annotations, and structural context for SCN5A F402C. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

21%

1/10 effective observations

Estimated BrS1 penetrance

13%

1/10 effective observations

Total carriers

0 BrS1 · 0 LQT3 · 0 unaffected

F402C has not been reported in gnomAD. This residue resides in a Non_Hotspot region for Brugada syndrome and a Mild_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	0.989	7	25

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 F402C.
Neighbour residue	Distance (Å)	Observed variants
403	6
1659	14
404	8	L404Q, L404V,
1765	10
396	9	V396L, V396A,
1653	12
391	15
372	14
1771	9	I1771T,
401	4	S401P,
1764	7	V1764F, c.5290delG,
371	8	Q371E,
409	12	L409V, L409P,
1711	14	c.5131delG,
928	14	L928P,
1650	12	L1650F,
260	14
366	14
1707	14
1656	13
365	14
1706	14	Q1706H,
1762	14	p.I1762del, I1762M,
1668	14	M1668T,
1466	13	c.4396_4397insG,
369	9	M369K,
1767	5	Y1767C,
1660	10	I1660S, I1660V,
1654	12
1769	11
402	0	F402L,
1766	11	M1766V, M1766L, M1766T,
1665	15
1768	8	I1768V,
1663	13
399	7
397	6	I397T, I397F, I397V,
405	7
1657	9
1759	11	S1759C,
261	14
1662	14
1709	9	T1709R, T1709M, p.T1709del,
392	14
1772	13	L1772V,
395	11
393	12
390	15
394	10
410	14	A410V,
1770	11	I1770V,
264	14
1658	12
1708	10	T1708I,
408	12
374	12	W374G,
1705	12
407	11
367	15	R367L, R367C, R367H,
1763	10	V1763L, V1763M,
1760	11
370	10	T370M,
1661	10	G1661R, G1661E
1761	14	L1761F, L1761H, c.5280delG,
1655	14
1469	15	I1469V,
406	7	N406S, N406K,
368	11
1710	12	S1710L,
932	14
398	5
257	14
400	6	G400R, G400A, G400E,
1664	10