SCN5A Variant I1749N
Summary of observed carriers, functional annotations, and structural context for SCN5A I1749N. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
53%
3/11 effective observations
Estimated BrS1 penetrance
16%
1/11 effective observations
Total carriers
1
0 BrS1 · 1 LQT3 · 0 unaffected
Variant features alone are equivalent to phenotyping 1 individuals for Brugada syndrome and 2 individuals for LQT3.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
|---|---|---|---|---|---|
| -6.47 | 1 | -4.36 | 0.959 | 14 | 59 |
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
| Source | Year | Carriers | Unaffected | LQT3 | BrS1 | Other | Other Disease |
|---|---|---|---|---|---|---|---|
| 30059973 | 2018 | 1 | 1 | 0 | 0 | ||
| Literature, cohort, and gnomAD | – | 1 | 0 | 1 | 0 | – | |
| Variant features alone | – | 15 | 12 | 2 | 1 | – | – |
Totals may differ from individual publications due to duplicate patients removed during curation.
Functional data
Peak and late/persistent current values are relative to wild-type (100% indicates no change). V1/2 activation and inactivation denote the membrane potentials (mV) at which half-maximal current is achieved.
| PubMed ID | Year | Cell Type | Peak Current (% WT) | V1/2 Activation (mV) | V1/2 Inactivation (mV) | Late/Persistent Current (% WT) |
|---|---|---|---|---|---|---|
| 30059973 | 2018 |
Nearby variants
Neighbouring residues within 15 Ångström provide structural context. Variants listed in the right-most column have been observed clinically or in gnomAD.
| Neighbour residue | Distance (Å) | Observed variants |
|---|---|---|
| 1746 | 5 | A1746T, A1746V, |
| 1724 | 14 | |
| 1417 | 15 | |
| 1406 | 10 | G1406R, G1406R, G1406E, |
| 1757 | 13 | |
| 1715 | 13 | |
| 1745 | 6 | |
| 1756 | 11 | I1756V, |
| 1675 | 13 | |
| 1743 | 12 | G1743R, G1743R, G1743E, |
| 1723 | 12 | T1723N, |
| 1754 | 9 | |
| 1707 | 14 | |
| 1694 | 15 | |
| 1411 | 12 | |
| 1407 | 10 | |
| 1410 | 7 | |
| 1747 | 6 | V1747M, |
| 1716 | 12 | p.L1716SfsX71, |
| 1714 | 12 | D1714G, |
| 1671 | 13 | |
| 1404 | 13 | |
| 1744 | 8 | S1744I, |
| 1721 | 7 | |
| 1753 | 6 | T1753A, |
| 1712 | 15 | G1712S, G1712C, |
| 1412 | 14 | L1412F, |
| 1719 | 12 | |
| 1408 | 12 | G1408R, G1408R, |
| 1758 | 15 | I1758V, p.I1758del |
| 1678 | 12 | N1678S, |
| 1755 | 12 | |
| 1401 | 14 | |
| 1674 | 13 | F1674V, |
| 1399 | 13 | |
| 1713 | 11 | |
| 1748 | 4 | p.G1748del, G1748D, |
| 1405 | 14 | V1405M, V1405L, V1405L, |
| 1409 | 10 | Y1409C, Y1409X, |
| 1400 | 13 | V1400I, |
| 1718 | 11 | S1718R, S1718R, S1718R, |
| 1717 | 8 | L1717P, |
| 1751 | 8 | |
| 1682 | 15 | |
| 1750 | 5 | L1750F, |
| 1752 | 7 | |
| 1722 | 10 | N1722D, |
| 1749 | 0 | I1749N, |
| 1720 | 9 | c.5157delC, |
| 1679 | 12 | |
| 1414 | 12 | Q1414H, Q1414H, |
| 1413 | 11 |