SCN5A Variant W1684R

Summary of observed carriers, functional annotations, and structural context for SCN5A W1684R. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

7%

0/11 effective observations

Estimated BrS1 penetrance

9%

1/11 effective observations

Total carriers

1

0 BrS1 · 0 LQT3 · 1 unaffected

W1684R is present in 1 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 (%)
0.2 0.117 0.57 0.562 9 0

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 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 W1684R.
Neighbour residue Distance (Å) Observed variants
333 13 c.998+1G>A, c.998+5G>A,
326 15
1741 10 D1741N, D1741Y, D1741E, D1741E,
1715 12
1687 8
1743 13 G1743E, G1743R, G1743R,
334 14 c.999-424_1338+81del,
1681 11 c.5040_5042delTTAinsC, Y1681F,
1694 12
1695 11 Q1695X,
1716 12 p.L1716SfsX71,
1688 5
1684 0 W1684R, W1684R,
1692 10
1721 15
1742 14
1693 9
1699 13
379 13
1680 12 A1680T, A1680P,
1703 14
1719 9
1690 5 c.5068_5070delGA, D1690N
324 13
383 12
1683 7
1718 12 S1718R, S1718R, S1718R,
1689 6 D1689N,
1739 12 R1739Q, R1739W,
1717 15 L1717P,
1682 9
336 14 P336L,
1686 8
1740 13 G1740R, G1740R,
1691 10
1720 12 c.5157delC,
1679 14
1685 6