SCN5A Variant G1420R
Summary of observed carriers, functional annotations, and structural context for SCN5A G1420R. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
3%
0/13 effective observations
Estimated BrS1 penetrance
70%
9/13 effective observations
Total carriers
3
3 BrS1 · 0 LQT3 · 0 unaffected
Variant features alone are equivalent to phenotyping 6 individuals for Brugada syndrome and 0 individuals for LQT3.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
|---|---|---|---|---|---|
| -7.59 | 1 | -4.79 | 0.968 | 92 | 2 |
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 |
|---|---|---|---|---|---|---|---|
| 26729854 | 2016 | 1 | 0 | 1 | 0 | ||
| 28341781 | 2017 | 1 | 0 | 1 | 0 | ||
| 20129283 | 2010 | 1 | 0 | 1 | 0 | ||
| 29574140 | 2018 | 1 | 0 | 1 | 0 | ||
| Literature, cohort, and gnomAD | – | 3 | 0 | 0 | 3 | – | |
| Variant features alone | – | 15 | 9 | 0 | 6 | – | – |
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 |
|---|---|---|
| 901 | 12 | S901L, E901K, |
| 896 | 12 | C896S, C896S, |
| 1417 | 9 | |
| 1430 | 15 | D1430N, |
| 1426 | 11 | |
| 1453 | 14 | |
| 1715 | 9 | |
| 1687 | 13 | |
| 372 | 13 | |
| 1756 | 15 | I1756V, |
| 1429 | 14 | |
| 1711 | 11 | c.5131delG, |
| 1450 | 12 | |
| 1707 | 14 | |
| 1398 | 12 | V1398M, |
| 1411 | 9 | |
| 1407 | 14 | |
| 1458 | 14 | S1458Y, |
| 1410 | 12 | |
| 1706 | 14 | Q1706H, Q1706H, |
| 1716 | 12 | p.L1716SfsX71, |
| 1714 | 6 | D1714G, |
| 376 | 13 | R376C, R376H, |
| 897 | 13 | G897R, G897E, G897R, |
| 1423 | 5 | D1423H, |
| 1721 | 15 | |
| 1422 | 6 | M1422R, |
| 1418 | 8 | |
| 892 | 14 | F892I, |
| 373 | 11 | |
| 1712 | 8 | G1712S, G1712C, |
| 898 | 9 | |
| 893 | 10 | R893H, R893C, |
| 1412 | 11 | L1412F, |
| 1719 | 14 | |
| 1408 | 13 | G1408R, G1408R, |
| 889 | 14 | |
| 1709 | 15 | p.T1709del, T1709R, T1709M, |
| 1420 | 0 | G1420D, G1420P, G1420V, G1420R, |
| 1360 | 13 | F1360C, |
| 1401 | 13 | |
| 1425 | 9 | |
| 1399 | 12 | |
| 1713 | 10 | |
| 1454 | 13 | |
| 1427 | 11 | A1427S, A1427E, |
| 1424 | 6 | I1424V, |
| 1409 | 15 | Y1409X, Y1409C, |
| 878 | 11 | R878C, R878H, R878L, |
| 1400 | 8 | V1400I, |
| 1421 | 5 | |
| 1718 | 11 | S1718R, S1718R, S1718R, |
| 1717 | 11 | L1717P, |
| 1416 | 10 | A1416E, c.4245+1G>C, A1416G, c.4245+2T>A, c.4245+1G>A, |
| 1752 | 14 | |
| 879 | 12 | W879R, W879R, |
| 1686 | 12 | |
| 375 | 12 | |
| 1710 | 11 | S1710L, |
| 1415 | 7 | |
| 1428 | 12 | A1428S, A1428V, |
| 1419 | 5 | K1419E, |
| 1414 | 6 | Q1414H, Q1414H, |
| 1402 | 13 | |
| 1413 | 11 |