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

7%

0/12 effective observations

Estimated BrS1 penetrance

9%

1/12 effective observations

Total carriers

2

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 R1644C, R1644H, R1644L,
1640 3
256 14
1793 12 M1793K,
1789 10
255 13
1645 10 T1645M,
1796 15
251 14
1638 6 R1638X, R1638Q,
1633 12
1637 6
253 14
1792 14 D1792N, D1792Y, D1792V,
1636 9
1823 13 E1823K, p.E1823HfsX10
1642 8 G1642E,
1528 14
1790 13 D1790N, D1790G, p.D1790del,
252 10
1647 12
1822 12 c.5464_5467delTCTG, c.5464-5467delTCTG,
1646 13
1782 14