SCN5A Variant G1748D
Summary of observed carriers, functional annotations, and structural context for SCN5A G1748D. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
28%
1/11 effective observations
Estimated BrS1 penetrance
38%
4/11 effective observations
Total carriers
1
1 BrS1 · 0 LQT3 · 0 unaffected
Variant features alone are equivalent to phenotyping 3 individuals for Brugada syndrome and 1 individuals for LQT3.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
|---|---|---|---|---|---|
| -6.48 | 1 | -3.51 | 0.982 | 34 | 44 |
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 | ||
| Literature, cohort, and gnomAD | – | 1 | 0 | 0 | 1 | – | |
| Variant features alone | – | 15 | 11 | 1 | 3 | – | – |
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 | 5 | A1746T, A1746V, |
| 1724 | 15 | |
| 1406 | 13 | G1406R, G1406R, G1406E, |
| 1757 | 14 | |
| 1715 | 12 | |
| 1687 | 15 | |
| 1745 | 6 | |
| 1756 | 11 | I1756V, |
| 1675 | 10 | |
| 1743 | 9 | G1743R, G1743R, G1743E, |
| 1723 | 13 | T1723N, |
| 1754 | 9 | |
| 1707 | 12 | |
| 1694 | 11 | |
| 1411 | 14 | |
| 1407 | 14 | |
| 1704 | 13 | L1704H, |
| 1410 | 10 | |
| 1747 | 4 | V1747M, |
| 1716 | 10 | p.L1716SfsX71, |
| 1714 | 12 | D1714G, |
| 1688 | 14 | |
| 1671 | 11 | |
| 1676 | 14 | M1676T, M1676I, M1676I, M1676I, |
| 1744 | 6 | S1744I, |
| 1721 | 6 | |
| 1753 | 7 | T1753A, |
| 1672 | 14 | S1672Y, |
| 1742 | 13 | |
| 1712 | 14 | G1712S, G1712C, |
| 1680 | 13 | A1680T, A1680P, |
| 1703 | 14 | |
| 1719 | 10 | |
| 1758 | 15 | I1758V, p.I1758del |
| 1678 | 9 | N1678S, |
| 1755 | 11 | |
| 1674 | 10 | F1674V, |
| 1399 | 14 | |
| 1713 | 11 | |
| 1748 | 0 | p.G1748del, G1748D, |
| 1683 | 15 | |
| 1409 | 14 | Y1409C, Y1409X, |
| 1400 | 14 | V1400I, |
| 1718 | 10 | S1718R, S1718R, S1718R, |
| 1700 | 15 | |
| 1717 | 7 | L1717P, |
| 1751 | 5 | |
| 1677 | 12 | |
| 1682 | 12 | |
| 1750 | 5 | L1750F, |
| 1752 | 5 | |
| 1722 | 10 | N1722D, |
| 1749 | 4 | I1749N, |
| 1720 | 6 | c.5157delC, |
| 1679 | 8 | |
| 1685 | 14 | |
| 1414 | 13 | Q1414H, Q1414H, |
| 1413 | 13 |