SCN5A Variant I1758V

Summary of observed carriers, functional annotations, and structural context for SCN5A I1758V. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

26%

1/11 effective observations

Estimated BrS1 penetrance

7%

0/11 effective observations

Total carriers

1

0 BrS1 · 0 LQT3 · 1 unaffected

I1758V is present in 1 alleles in gnomAD. This residue resides in a Non_Hotspot region for Brugada syndrome and a 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 (%)
-0.79 0.894 0.88 0.793 4 44

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 I1758V.
Neighbour residue Distance (Å) Observed variants
1328 12 V1328M,
1417 14
1765 10
1757 4
1413 15
1756 7 I1756V,
1320 15 M1320I, M1320I, M1320I,
1764 9 c.5290delG, V1764F,
1666 11
1333 14
1754 6
1707 11
1704 12 L1704H,
1669 14
1671 8
1762 5 p.I1762del, I1762M,
1668 11 M1668T,
1466 14 c.4396_4397insG,
1753 9 T1753A,
1672 14 S1672Y,
1767 14 Y1767C,
1660 12 I1660V, I1660S,
1329 13 G1329S,
1766 10 M1766L, M1766V, M1766L, M1766T,
1665 14
1768 15 I1768V
1334 10 I1334V,
1468 14 V1468F, V1468A,
1663 9
1462 14
1759 5 S1759C,
1662 15
1324 12
1327 9
1709 13 p.T1709del, T1709R, T1709M,
1758 0 I1758V, p.I1758del,
1755 6
1330 11 A1330T, A1330P, A1330D,
1674 13 F1674V,
1713 12
1323 13 V1323G,
1338 12 L1338V,
1748 15 p.G1748del, G1748D,
1708 10 T1708I,
1705 15
1337 14
1326 13 A1326S,
1763 6 V1763M, V1763L, V1763L,
1751 11
1311 13 L1311P,
1332 14 P1332Q, P1332L,
1308 14 L1308F,
1465 11 p.F1465_L1480dup,
1760 9
1750 12 L1750F,
1752 11
1670 11
1661 13 G1661R, G1661R, G1661E,
1331 10 I1331V,
1761 7 c.5280delG, L1761F, L1761H,
1749 15 I1749N,
1469 12 I1469V,
1710 12 S1710L,
1335 13 M1335R,
1667 7 V1667I,
1664 9