SCN5A Variant S1744I

Summary of observed carriers, functional annotations, and structural context for SCN5A S1744I. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

7%

0/12 effective observations

Estimated BrS1 penetrance

19%

2/12 effective observations

Total carriers

2

0 BrS1 · 0 LQT3 · 2 unaffected

S1744I is present in 2 alleles in gnomAD. This residue resides in a Hotspot region for Brugada syndrome and a Mild_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 (%)
-4.33 1 -2.91 0.853 25 12

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 – 2 2 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 S1744I.
Neighbour residue Distance (Å) Observed variants
1746 6 A1746T, A1746V,
1724 12
1741 11 D1741N, D1741Y, D1741E, D1741E,
1715 13
1687 15
1745 4
1675 10
1743 4 G1743R, G1743R, G1743E,
1723 11 T1723N,
1754 14
1725 13 P1725L,
1681 13 c.5040_5042delTTAinsC, Y1681F,
1694 11
1410 14
1747 5 V1747M,
1716 12 p.L1716SfsX71,
1695 15 Q1695X,
1714 14 D1714G,
1688 13
1671 15
1676 13 M1676T, M1676I, M1676I, M1676I,
1744 0 S1744I,
1721 5
1753 13 T1753A
1742 7
1693 14
1680 10 A1680T, A1680P,
1719 8
1731 12
1728 12 C1728R, C1728Y, C1728W,
1678 8 N1678S,
1300 14
1674 12 F1674V,
1399 13
1748 6 p.G1748del, G1748D,
1730 15 P1730A, P1730H, P1730L,
1683 10
1718 10 S1718R, S1718R, S1718R,
1739 14 R1739W, R1739Q,
1717 9 L1717P,
1751 10
1677 11
1682 8
1750 10 L1750F,
1752 10
1722 6 N1722D,
1686 14
1749 8 I1749N,
1729 15 D1729N,
1740 11 G1740R, G1740R,
1720 5 c.5157delC,
1732 12
1679 7
1685 12