SCN5A Variant D1690N
Summary of observed carriers, functional annotations, and structural context for SCN5A D1690N. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
3%
0/13 effective observations
Estimated BrS1 penetrance
52%
6/13 effective observations
Total carriers
3
2 BrS1 · 0 LQT3 · 1 unaffected
Variant features alone are equivalent to phenotyping 4 individuals for Brugada syndrome and 0 individuals for LQT3.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
|---|---|---|---|---|---|
| -4.79 | 1 | -0.31 | 0.838 | 72 | 0 |
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 |
|---|---|---|---|---|---|---|---|
| 23085483 | 2013 | 1 | 0 | 1 | 0 | ||
| 26173111 | 2015 | 1 | 0 | 1 | 0 | ||
| 29325976 | 2018 | 1 | 0 | 1 | 0 | ||
| Literature, cohort, and gnomAD | – | 3 | 1 | 0 | 2 | – | |
| Variant features alone | – | 15 | 11 | 0 | 4 | – | – |
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.
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 |
|---|---|---|
| 333 | 8 | c.998+1G>A, c.998+5G>A, |
| 1702 | 13 | |
| 326 | 12 | |
| 387 | 14 | |
| 1741 | 12 | D1741N, D1741Y, D1741E, D1741E, |
| 1715 | 15 | |
| 1687 | 10 | |
| 330 | 14 | S330F, |
| 1698 | 13 | A1698T, |
| 334 | 9 | c.999-424_1338+81del, |
| 332 | 11 | A332T, |
| 1681 | 10 | c.5040_5042delTTAinsC, Y1681F, |
| 1694 | 11 | |
| 327 | 14 | |
| 1695 | 8 | Q1695X, |
| 384 | 15 | S384T, |
| 1716 | 13 | p.L1716SfsX71, |
| 1688 | 7 | |
| 1684 | 5 | W1684R, W1684R, |
| 329 | 15 | |
| 1676 | 15 | M1676I, M1676I, M1676I, M1676T, |
| 1692 | 8 | |
| 386 | 15 | G386E, G386R, G386R, |
| 1693 | 6 | |
| 1699 | 9 | |
| 331 | 11 | |
| 379 | 12 | |
| 1680 | 12 | A1680T, A1680P, |
| 1703 | 12 | |
| 1719 | 12 | |
| 335 | 12 | C335S, C335R, C335S, |
| 325 | 14 | L325R, |
| 1228 | 13 | Y1228C, Y1228F, Y1228H, |
| 1690 | 0 | c.5068_5070delGA, D1690N |
| 324 | 12 | |
| 1227 | 12 | |
| 383 | 10 | |
| 1683 | 10 | |
| 382 | 13 | |
| 1696 | 11 | |
| 1689 | 5 | D1689N, |
| 1739 | 14 | R1739Q, R1739W, |
| 1700 | 13 | |
| 1682 | 11 | |
| 336 | 12 | P336L, |
| 1686 | 12 | |
| 1740 | 15 | G1740R, G1740R, |
| 1691 | 6 | |
| 1720 | 15 | c.5157delC, |
| 1679 | 14 | |
| 1685 | 11 |