SCN5A Variant I1756V

Summary of observed carriers, functional annotations, and structural context for SCN5A I1756V. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

12%

0/11 effective observations

Estimated BrS1 penetrance

6%

0/11 effective observations

Total carriers

1

0 BrS1 · 0 LQT3 · 1 unaffected

I1756V 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 0 individuals for LQT3.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density BrS (%) Penetrance Density LQT3 (%)
-0.93 0.998 3.24 0.858 4 16

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 15 0 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 I1756V.
Neighbour residue Distance (Å) Observed variants
1746 15 A1746T, A1746V,
1417 8
1765 12
1457 15
1757 5
1715 14
1413 9
1756 0 I1756V,
1461 14 T1461S, T1461S,
1764 11 c.5290delG, V1764F,
1711 11 c.5131delG,
1754 6
1707 8
1411 13
1704 11 L1704H,
1458 14 S1458Y,
1410 11
1706 13 Q1706H, Q1706H,
1747 14 V1747M,
1716 12 p.L1716SfsX71,
1714 12 D1714G,
1671 11
1762 9 p.I1762del, I1762M,
1668 13 M1668T,
1466 15 c.4396_4397insG,
1753 5 T1753A,
1418 13
1766 14 M1766L, M1766V, M1766L, M1766T
1712 11 G1712S, G1712C,
1703 14
1334 13 I1334V,
1341 13
1663 15
1462 11
1412 14 L1412F,
1759 6 S1759C,
1709 10 p.T1709del, T1709R, T1709M,
1420 15 G1420R, G1420D, G1420V, G1420P,
1758 7 I1758V, p.I1758del,
1755 5
1674 15 F1674V,
1713 6
1338 12 L1338V,
1748 11 p.G1748del, G1748D,
1708 9 T1708I,
1409 12 Y1409C, Y1409X,
1705 14
1345 13 W1345C, W1345C,
1337 14
1717 11 L1717P,
1342 14
1763 11 V1763M, V1763L, V1763L,
1751 9
1416 11 c.4245+1G>A, c.4245+1G>C, c.4245+2T>A, A1416E, A1416G,
1465 11 p.F1465_L1480dup,
1760 6
1750 11 L1750F,
1752 7
1670 15
1331 15 I1331V,
1761 6 c.5280delG, L1761F, L1761H,
1749 11 I1749N,
1710 8 S1710L,
1720 15 c.5157delC,
1415 13
1419 11 K1419E,
1667 12 V1667I,
1414 10 Q1414H, Q1414H,
1664 13
1463 14 N1463Y,