SCN5A Variant S1718R

Summary of observed carriers, functional annotations, and structural context for SCN5A S1718R. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

3%

0/11 effective observations

Estimated BrS1 penetrance

21%

2/11 effective observations

Total carriers

1

0 BrS1 · 0 LQT3 · 1 unaffected

S1718R is present in 1 alleles in gnomAD. This residue resides in a Mild_Hotspot region for Brugada syndrome and a Non_Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 2 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 (%)
-2.83 0.942 -1.48 0.687 30 1

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 13 0 2 – –

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 S1718R.
Neighbour residue Distance (Å) Observed variants
1746 13 A1746T, A1746V,
1724 13
1741 14 D1741N, D1741Y, D1741E, D1741E,
1715 5
1687 9
1745 10
1397 13 c.4189delT, c.4190delA,
1743 11 G1743R, G1743R, G1743E,
1711 14 c.5131delG,
1723 9 T1723N,
1707 14
1725 13 P1725L,
1398 11 V1398M,
1694 13
1411 12
1407 13
1410 11
1706 15 Q1706H, Q1706H,
1747 13 V1747M,
1716 7 p.L1716SfsX71,
1714 6 D1714G,
1688 10
1684 12 W1684R, W1684R,
1423 12 D1423H,
1692 15
1744 10 S1744I,
1721 5
1753 14 T1753A
1742 14
1693 15
1712 10 G1712S, G1712C,
1703 14
1719 4
1408 15 G1408R, G1408R,
1420 11 G1420R, G1420D, G1420V, G1420P,
1401 12
1399 6
1713 11
1424 13 I1424V,
1748 10 p.G1748del, G1748D,
1683 11
1400 9 V1400I,
1718 0 S1718R, S1718R, S1718R,
1689 14 D1689N,
1717 5 L1717P,
1751 13
1682 11
1750 15 L1750F,
1752 10
1722 9 N1722D,
1686 7
1749 11 I1749N,
375 14
1720 6 c.5157delC,
1679 12
1685 7
1419 13 K1419E,
1414 11 Q1414H, Q1414H,
1413 14