SCN5A Variant S1759C

Summary of observed carriers, functional annotations, and structural context for SCN5A S1759C. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

27%

1/11 effective observations

Estimated BrS1 penetrance

7%

0/11 effective observations

Total carriers

1

0 BrS1 · 0 LQT3 · 1 unaffected

S1759C 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 1 individuals for LQT3.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density BrS (%) Penetrance Density LQT3 (%)
-4.57 0.923 6.64 0.84 8 31

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 1 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 S1759C.
Neighbour residue Distance (Å) Observed variants
1417 12
1765 8
1757 7
1413 15
401 15 S401P,
1756 6 I1756V,
1764 6 c.5290delG, V1764F,
1666 12
371 13 Q371E,
1711 11 c.5131delG,
1754 9
1707 8
1704 10 L1704H,
1706 12 Q1706H, Q1706H,
1669 14
1671 10
1762 6 p.I1762del, I1762M,
1668 9 M1668T,
1466 13 c.4396_4397insG,
1753 11 T1753A,
1672 14 S1672Y,
1767 11 Y1767C,
1660 10 I1660V, I1660S,
1769 14
402 11 F402L, F402L, F402L,
1766 9 M1766L, M1766V, M1766L, M1766T,
1665 12
1768 12 I1768V
1712 14 G1712S, G1712C,
1703 14
1334 13 I1334V,
1663 9
397 14 I397V, I397F, I397T,
1462 13
1657 14
1759 0 S1759C,
1662 14
1324 14
1327 11
1709 8 p.T1709del, T1709R, T1709M,
1701 14 M1701I, M1701I, M1701I,
1758 5 I1758V, p.I1758del,
1755 5
1330 14 A1330T, A1330P, A1330D,
1713 10
1323 13 V1323G,
1338 15 L1338V,
394 15
1708 5 T1708I,
374 14 W374G,
1705 11
1700 15
1326 14 A1326S,
1763 5 V1763M, V1763L, V1763L,
1751 12
1416 15 c.4245+1G>A, c.4245+1G>C, c.4245+2T>A, A1416E, A1416G,
1465 11 p.F1465_L1480dup,
1760 6
1752 11
1670 12
1661 11 G1661R, G1661R, G1661E,
1331 13 I1331V,
1761 7 c.5280delG, L1761F, L1761H,
1469 12 I1469V,
1710 9 S1710L,
398 13
1419 15 K1419E,
1667 8 V1667I,
1664 7
1463 15 N1463Y,