SCN5A Variant G1743R
Summary of observed carriers, functional annotations, and structural context for SCN5A G1743R. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
2%
0/28 effective observations
Estimated BrS1 penetrance
59%
16/28 effective observations
Total carriers
18
12 BrS1 · 0 LQT3 · 6 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 (%) |
|---|---|---|---|---|---|
| -7.4 | 1 | -2.88 | 0.974 | 60 | 3 |
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 |
|---|---|---|---|---|---|---|---|
| 15023552 | 2004 | 3 | 0 | 1 | 0 | ||
| 12639704 | 2003 | 1 | 0 | 1 | 0 | ||
| 22984773 | 2013 | 10 | 0 | 6 | 0 | ||
| 26111534 | 2015 | 1 | 0 | 0 | 1 | SND, AT, AVB, LVNC, VT | |
| 28341781 | 2017 | 1 | 0 | 1 | 0 | ||
| 21126620 | 2010 | 1 | 0 | 1 | 0 | ||
| 20129283 | 2010 | 1 | 0 | 1 | 0 | ||
| 20129283 | 2010 | 1 | 0 | 1 | 0 | ||
| 20129283 | 2010 | 1 | 0 | 1 | 0 | ||
| 20129283 | 2010 | 1 | 0 | 1 | 0 | ||
| 30059973 | 2018 | 3 | 3 | 0 | 0 | ||
| Literature, cohort, and gnomAD | – | 18 | 6 | 0 | 12 | – | |
| 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.
| PubMed ID | Year | Cell Type | Peak Current (% WT) | V1/2 Activation (mV) | V1/2 Inactivation (mV) | Late/Persistent Current (% WT) |
|---|---|---|---|---|---|---|
| 12639704 | 2003 | |||||
| 22984773 | 2013 | |||||
| 26111534 | 2015 | |||||
| 28341781 | 2017 | |||||
| 21126620 | 2010 | |||||
| 20129283 | 2010 | |||||
| 20129283 | 2010 | |||||
| 20129283 | 2010 | |||||
| 20129283 | 2010 | |||||
| 30059973 | 2018 | |||||
| 15023552 | 2004 | HEK | 0 |
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 | 10 | A1746V, A1746T, |
| 1724 | 12 | |
| 1741 | 7 | D1741N, D1741Y, D1741E, D1741E, |
| 1715 | 14 | |
| 1687 | 15 | |
| 1726 | 15 | |
| 1745 | 7 | |
| 1675 | 12 | |
| 1743 | 0 | G1743E, G1743R, G1743R, |
| 1723 | 11 | T1723N, |
| 1725 | 11 | P1725L, |
| 1681 | 11 | c.5040_5042delTTAinsC, Y1681F, |
| 1694 | 12 | |
| 1747 | 8 | V1747M, |
| 1716 | 13 | p.L1716SfsX71, |
| 1695 | 14 | Q1695X, |
| 1688 | 13 | |
| 1684 | 13 | W1684R, W1684R, |
| 1676 | 14 | M1676I, M1676I, M1676I, M1676T, |
| 1744 | 4 | S1744I, |
| 1721 | 7 | |
| 1742 | 4 | |
| 1733 | 13 | |
| 1693 | 14 | |
| 1738 | 14 | S1738T, S1738F, |
| 1680 | 9 | A1680T, A1680P, |
| 1727 | 14 | |
| 1719 | 8 | |
| 1731 | 8 | |
| 1728 | 10 | C1728Y, C1728W, C1728R, |
| 1678 | 9 | N1678S, |
| 1300 | 15 | |
| 1674 | 15 | F1674V, |
| 1399 | 13 | |
| 1748 | 9 | G1748D, p.G1748del, |
| 1730 | 12 | P1730A, P1730L, P1730H, |
| 1683 | 7 | |
| 1718 | 11 | S1718R, S1718R, S1718R, |
| 1739 | 11 | R1739Q, R1739W, |
| 1717 | 11 | L1717P, |
| 1734 | 14 | |
| 1751 | 13 | |
| 1677 | 12 | |
| 1682 | 6 | |
| 1750 | 14 | L1750F, |
| 1752 | 14 | |
| 1722 | 6 | N1722D, |
| 1686 | 14 | |
| 1749 | 12 | I1749N, |
| 1729 | 12 | D1729N, |
| 1740 | 7 | G1740R, G1740R, |
| 1720 | 6 | c.5157delC, |
| 1732 | 9 | |
| 1679 | 8 | |
| 1685 | 11 |