SCN5A Variant T1708I

Summary of observed carriers, functional annotations, and structural context for SCN5A T1708I. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

7%

0/11 effective observations

Estimated BrS1 penetrance

28%

3/11 effective observations

Total carriers

1

0 BrS1 · 0 LQT3 · 1 unaffected

T1708I is present in 1 alleles in gnomAD. This residue resides in a Hotspot region for Brugada syndrome and a Non_Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 3 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 (%)
-5.45 1 -1.15 0.895 42 5

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 12 0 3

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 T1708I.
Neighbour residue Distance (Å) Observed variants
1702 11
1417 12
1765 11
396 14 V396L, V396A,
1757 11
1715 15
372 15
1698 15 A1698T,
401 12 S401P,
1756 9 I1756V,
1764 8 c.5290delG, V1764F,
1666 13
371 10 Q371E,
1711 8 c.5131delG,
1754 12
1707 5
1694 14
1704 6 L1704H,
1706 7 Q1706H, Q1706H,
1716 12 p.L1716SfsX71,
1669 14
1671 11
1762 11 p.I1762del, I1762M,
1668 7 M1668T,
1692 14
1753 13 T1753A,
1672 12 S1672Y,
1767 12 Y1767C,
1660 12 I1660V, I1660S,
378 12
1699 15
402 10 F402L, F402L, F402L,
1766 13 M1766L, M1766V, M1766L, M1766T,
1665 11
373 14
1768 14 I1768V
1712 10 G1712S, G1712C,
379 15
1703 9
1663 11
399 15
397 10 I397V, I397F, I397T,
1657 15
1759 5 S1759C,
1662 14
1709 4 p.T1709del, T1709R, T1709M,
1701 10 M1701I, M1701I, M1701I,
1758 10 I1758V, p.I1758del,
1755 6
393 13
1713 8
390 13
394 11
1708 0 T1708I,
374 10 W374G,
1705 6
1700 12
1717 14 L1717P,
1763 9 V1763M, V1763L, V1763L,
1751 12
1760 8
370 15 T370M,
1752 11
1670 13
1661 11 G1661R, G1661R, G1661E,
1761 11 c.5280delG, L1761F, L1761H,
375 12
368 14
1710 7 S1710L,
398 11
400 15 G400R, G400R, G400E, G400A,
1419 13 K1419E,
1667 9 V1667I,
1664 7