SCN5A Variant G1639A

Summary of observed carriers, functional annotations, and structural context for SCN5A G1639A. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

0/12 effective observations

Estimated BrS1 penetrance

1/12 effective observations

Total carriers

0 BrS1 · 0 LQT3 · 2 unaffected

G1639A is present in 2 alleles in gnomAD. This residue resides in a Non_Hotspot region for Brugada syndrome and a Non_Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 1 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 (%)
-3.7	0.967	0.39	0.59	8	5

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	–	2	2	0	0		–
Variant features alone	–	15	14	0	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 G1639A.
Neighbour residue	Distance (Å)	Observed variants
1643	9	I1643L,
1635	13
1634	12	L1634P,
1641	5
1639	0	G1639A
1787	14	S1787N,
1648	14
1532	14	V1532I, V1532F,
1644	7	R1644L, R1644C, R1644H,
1640	3
256	14
1793	12	M1793K,
1789	10
255	13
1645	10	T1645M,
1796	15
251	14
1638	6	R1638Q, R1638X,
1633	12
1637	6
253	14
1792	14	D1792N, D1792V, D1792Y,
1636	9
1823	13	E1823K, p.E1823HfsX10,
1642	8	G1642E,
1528	14
1790	13	D1790G, D1790N, p.D1790del,
252	10
1647	12
1822	12	c.5464_5467delTCTG, c.5464-5467delTCTG,
1646	13
1782	14