SCN5A Variant L939F

Summary of observed carriers, functional annotations, and structural context for SCN5A L939F. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

11%

0/11 effective observations

Estimated BrS1 penetrance

0/11 effective observations

Total carriers

0 BrS1 · 0 LQT3 · 1 unaffected

L939F is present in 1 alleles 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 0 individuals for Brugada syndrome and 0 individuals for LQT3.

In silico predictors

Variant-level computational predictors.
PROVEAN	PolyPhen-2	BLAST-PSSM	REVEL	Penetrance Density BrS (%)	Penetrance Density LQT3 (%)
-3.68	0.999	-0.72	0.872	3	16

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	–	1	1	0	0		–
Variant features alone	–	15	15	0	0	–	–

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 L939F.
Neighbour residue	Distance (Å)	Observed variants
414	12	M414V,
939	0	L939F,
937	7
1773	11
1765	13
839	13	L839P,
842	14
943	7	S943N,
1472	12	N1472S, p.N1472del,
1771	14	I1771T,
1461	13	T1461S,
418	14	E418K,
409	10	L409V, L409P,
1333	15
417	9
934	9
933	10
1471	7
935	7	L935P,
412	11	V412D,
1470	7
1464	9	L1464P, c.4389_4396delCCTCTTTA,
1466	8	c.4396_4397insG,
1776	12
944	10
1769	11
415	12	A415T,
1768	12	I1768V,
940	5	S940N,
1473	13	F1473C, F1473S,
1468	9	V1468A, V1468F,
831	12
1462	14
420	11
1474	11
938	5
942	7
419	15	Q419X,
930	14	c.2787+17_2787+18insACACACACACACACACACACACA, c.2788-6C>T,
1459	15	c.4376_4379delTCTT,
834	15	N834D,
1772	10	L1772V,
1460	12	F1460L,
239	15	I239V, I239V ,
410	11	A410V,
242	15	A242D,
1770	15	I1770V,
416	9	Y416C,
413	8	A413E, A413T,
941	7	S941N, S941F,
1337	15
936	5
238	15
838	13
1465	12	p.F1465_L1480dup,
1467	6
1775	14	p.F1775LfsX15, F1775V,
421	13
1475	14	p.Q1475NfsX6, Q1475L,
1469	10	I1469V,
406	14	N406S, N406K,
411	13	V411M,
932	11
832	14
835	13	S835A, S835L,
828	14	L828V,
931	13
1463	10	N1463Y,