SCN5A Variant G1712C
Summary of observed carriers, functional annotations, and structural context for SCN5A G1712C. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
5%
0/11 effective observations
Estimated BrS1 penetrance
57%
6/11 effective observations
Total carriers
1
1 BrS1 · 0 LQT3 · 0 unaffected
Variant features alone are equivalent to phenotyping 5 individuals for Brugada syndrome and 0 individuals for LQT3.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
|---|---|---|---|---|---|
| -8.33 | 1 | -3.96 | 0.967 | 74 | 1 |
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 |
|---|---|---|---|---|---|---|---|
| 28219873 | 2016 | 1 | 0 | 1 | 0 | ||
| Literature, cohort, and gnomAD | – | 1 | 0 | 0 | 1 | – | |
| Variant features alone | – | 15 | 10 | 0 | 5 | – | – |
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) |
|---|---|---|---|---|---|---|
| 28219873 | 2016 | 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 |
|---|---|---|
| 1702 | 13 | |
| 901 | 15 | S901L, E901K, |
| 1417 | 10 | |
| 1715 | 5 | |
| 1687 | 8 | |
| 1413 | 13 | |
| 372 | 12 | |
| 1756 | 11 | I1756V, |
| 371 | 12 | Q371E, |
| 1711 | 4 | c.5131delG, |
| 1707 | 7 | |
| 1694 | 13 | |
| 1411 | 14 | |
| 1704 | 11 | L1704H, |
| 1410 | 14 | |
| 1706 | 6 | Q1706H, Q1706H, |
| 1716 | 5 | p.L1716SfsX71, |
| 1714 | 6 | D1714G, |
| 376 | 10 | R376C, R376H, |
| 1688 | 11 | |
| 897 | 14 | G897E, G897R, G897R, |
| 1423 | 12 | D1423H, |
| 1692 | 11 | |
| 1721 | 13 | |
| 1753 | 14 | T1753A, |
| 1422 | 13 | M1422R, |
| 1693 | 14 | |
| 378 | 11 | |
| 1418 | 11 | |
| 373 | 9 | |
| 1712 | 0 | G1712C, G1712S, |
| 379 | 10 | |
| 1703 | 9 | |
| 898 | 12 | |
| 1759 | 14 | S1759C, |
| 1719 | 11 | |
| 1709 | 9 | T1709R, T1709M, p.T1709del, |
| 1420 | 8 | G1420D, G1420P, G1420R, G1420V, |
| 1755 | 12 | |
| 1399 | 14 | |
| 1713 | 5 | |
| 1424 | 14 | I1424V, |
| 1748 | 14 | G1748D, p.G1748del, |
| 1708 | 10 | T1708I, |
| 1400 | 14 | V1400I, |
| 1421 | 12 | |
| 1718 | 10 | S1718R, S1718R, S1718R, |
| 374 | 9 | W374G, |
| 1705 | 12 | |
| 1689 | 13 | D1689N, |
| 1700 | 14 | |
| 1717 | 8 | L1717P, |
| 367 | 14 | R367C, R367H, R367L, |
| 1751 | 13 | |
| 1416 | 13 | c.4245+2T>A, A1416G, c.4245+1G>A, c.4245+1G>C, A1416E, |
| 1760 | 12 | |
| 1752 | 9 | |
| 1686 | 10 | |
| 1749 | 15 | I1749N, |
| 375 | 6 | |
| 1691 | 15 | |
| 368 | 15 | |
| 1710 | 7 | S1710L, |
| 380 | 14 | |
| 1720 | 12 | c.5157delC, |
| 1415 | 13 | |
| 377 | 13 | |
| 1685 | 13 | |
| 1419 | 6 | K1419E, |
| 1414 | 9 | Q1414H, Q1414H, |