SCN5A Variant N1722D
Summary of observed carriers, functional annotations, and structural context for SCN5A N1722D. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
5%
0/18 effective observations
Estimated BrS1 penetrance
33%
5/18 effective observations
Total carriers
8
3 BrS1 · 0 LQT3 · 5 unaffected
Variant features alone are equivalent to phenotyping 2 individuals for Brugada syndrome and 0 individuals for LQT3.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
|---|---|---|---|---|---|
| -4.46 | 0.986 | 1.75 | 0.741 | 37 | 8 |
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 |
|---|---|---|---|---|---|---|---|
| 20031634 | 2009 | 8 | 0 | 3 | 0 | ||
| 20129283 | 2010 | 1 | 0 | 1 | 0 | ||
| 30059973 | 2018 | 2 | 2 | 0 | 0 | ||
| Literature, cohort, and gnomAD | – | 8 | 5 | 0 | 3 | – | |
| Variant features alone | – | 15 | 13 | 0 | 2 | – | – |
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 |
|---|---|---|
| 1746 | 9 | A1746T, A1746V, |
| 1724 | 6 | |
| 1741 | 12 | D1741N, D1741Y, D1741E, D1741E, |
| 1406 | 14 | G1406R, G1406R, G1406E, |
| 1715 | 14 | |
| 1726 | 11 | |
| 1745 | 5 | |
| 1397 | 13 | c.4189delT, c.4190delA, |
| 1743 | 6 | G1743R, G1743R, G1743E, |
| 1723 | 5 | T1723N, |
| 1725 | 7 | P1725L, |
| 1398 | 14 | V1398M, |
| 1407 | 13 | |
| 1410 | 13 | |
| 1747 | 10 | V1747M, |
| 1716 | 14 | p.L1716SfsX71, |
| 1714 | 14 | D1714G, |
| 1404 | 15 | |
| 1744 | 6 | S1744I, |
| 1721 | 5 | |
| 1742 | 8 | |
| 1680 | 14 | A1680T, A1680P, |
| 1727 | 12 | |
| 1719 | 9 | |
| 1731 | 11 | |
| 1728 | 8 | C1728R, C1728Y, C1728W, |
| 1678 | 14 | N1678S, |
| 1401 | 13 | |
| 1399 | 9 | |
| 1748 | 10 | p.G1748del, G1748D, |
| 1730 | 13 | P1730A, P1730H, P1730L, |
| 1683 | 11 | |
| 1400 | 13 | V1400I, |
| 1718 | 9 | S1718R, S1718R, S1718R, |
| 1717 | 10 | L1717P, |
| 1751 | 15 | |
| 1682 | 11 | |
| 1750 | 13 | L1750F |
| 1752 | 14 | |
| 1722 | 0 | N1722D, |
| 1686 | 14 | |
| 1749 | 10 | I1749N, |
| 1729 | 12 | D1729N, |
| 1740 | 13 | G1740R, G1740R, |
| 1720 | 8 | c.5157delC, |
| 1732 | 13 | |
| 1679 | 12 | |
| 1685 | 12 |