SCN5A Variant I1643L
Summary of observed carriers, functional annotations, and structural context for SCN5A I1643L. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
11%
0/11 effective observations
Estimated BrS1 penetrance
14%
1/11 effective observations
Total carriers
1
0 BrS1 · 0 LQT3 · 1 unaffected
Variant features alone are equivalent to phenotyping 1 individuals for Brugada syndrome and 0 individuals for LQT3.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
|---|---|---|---|---|---|
| -1.85 | 0.943 | 3.55 | 0.915 | 20 | 14 |
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 |
|---|---|---|---|---|---|---|---|
| Literature, cohort, and gnomAD | – | 1 | 1 | 0 | 0 | – | |
| Variant features alone | – | 15 | 14 | 0 | 1 | – | – |
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.
| Neighbour residue | Distance (Å) | Observed variants |
|---|---|---|
| 403 | 14 | |
| 414 | 14 | M414V, |
| 1643 | 0 | I1643L, |
| 404 | 12 | L404V, L404Q, |
| 1778 | 12 | |
| 249 | 11 | K249X, |
| 1635 | 14 | |
| 254 | 10 | |
| 1771 | 14 | I1771T, |
| 1652 | 14 | M1652T, M1652R, |
| 1634 | 9 | L1634P, |
| 250 | 10 | |
| 1650 | 10 | L1650F, |
| 260 | 12 | |
| 1641 | 8 | |
| 258 | 12 | V258A, |
| 1639 | 9 | G1639A, |
| 1779 | 12 | T1779M, |
| 1787 | 14 | S1787N, |
| 1648 | 10 | |
| 1649 | 10 | A1649V, |
| 1774 | 15 | N1774D, c.5321_5324dupACTT, |
| 1644 | 7 | R1644C, R1644H, R1644L, |
| 1640 | 6 | |
| 256 | 7 | |
| 248 | 15 | |
| 1789 | 12 | |
| 255 | 8 | |
| 1645 | 6 | T1645M, |
| 251 | 9 | |
| 410 | 13 | A410V, |
| 1788 | 15 | c.5361_5364delTGAG |
| 1638 | 11 | R1638X, R1638Q, |
| 1651 | 12 | |
| 259 | 11 | |
| 1633 | 11 | |
| 1637 | 6 | |
| 408 | 13 | |
| 253 | 7 | |
| 1636 | 11 | |
| 407 | 10 | |
| 1775 | 11 | F1775V, p.F1775LfsX15, |
| 1642 | 4 | G1642E, |
| 1631 | 14 | G1631D, |
| 252 | 6 | |
| 411 | 12 | V411M, |
| 1647 | 5 | |
| 257 | 10 | |
| 1646 | 5 | |
| 1782 | 13 |