SCN5A Variant G1406R
Summary of observed carriers, functional annotations, and structural context for SCN5A G1406R. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
1%
0/15 effective observations
Estimated BrS1 penetrance
67%
10/15 effective observations
Total carriers
5
4 BrS1 · 0 LQT3 · 1 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 (%) |
|---|---|---|---|---|---|
| -6.48 | 1 | -4.09 | 0.981 | 88 | 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 |
|---|---|---|---|---|---|---|---|
| 11748104 | 2001 | 13 | 0 | 4 | 8 | CCCD | |
| 12106943 | 2002 | 1 | 0 | 1 | 0 | ||
| 26921764 | 2016 | 1 | 0 | 1 | 0 | ||
| 20129283 | 2010 | 1 | 0 | 1 | 0 | ||
| 29325976 | 2018 | 1 | 0 | 1 | 0 | ||
| 30059973 | 2018 | 2 | 2 | 0 | 0 | ||
| Literature, cohort, and gnomAD | – | 5 | 1 | 0 | 4 | – | |
| 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.
| PubMed ID | Year | Cell Type | Peak Current (% WT) | V1/2 Activation (mV) | V1/2 Inactivation (mV) | Late/Persistent Current (% WT) |
|---|---|---|---|---|---|---|
| 29325976 | 2018 | |||||
| 16632547 | 2006 | HEK | 8 | 3.4 | -6.3 | |
| 30059973 | 2018 | |||||
| 11748104 | 2001 | COS | 0 | |||
| 11748091 | 2001 | |||||
| 12106943 | 2002 | |||||
| 14716629 | 2003 | |||||
| 26921764 | 2016 | |||||
| 20129283 | 2010 |
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 |
|---|---|---|
| 1403 | 9 | |
| 1746 | 12 | A1746V, A1746T, |
| 1357 | 12 | A1357V, |
| 1724 | 14 | |
| 1352 | 11 | |
| 1406 | 0 | G1406R, G1406R, G1406E, |
| 1453 | 15 | |
| 1351 | 14 | M1351V, M1351R, |
| 739 | 13 | |
| 1745 | 13 | |
| 1397 | 14 | c.4189delT, c.4190delA, |
| 1350 | 11 | I1350T, I1350L, |
| 1723 | 12 | T1723N, |
| 731 | 15 | T731I, |
| 1398 | 14 | V1398M, |
| 1411 | 8 | |
| 1353 | 10 | V1353M |
| 1407 | 3 | |
| 737 | 12 | |
| 1410 | 6 | |
| 1714 | 15 | D1714G, |
| 1358 | 14 | G1358R, G1358W, G1358R, |
| 1348 | 13 | F1348L, F1348L, F1348L, |
| 1404 | 5 | |
| 1721 | 13 | |
| 1349 | 8 | |
| 1753 | 12 | T1753A, |
| 1346 | 10 | L1346I, L1346P, |
| 1341 | 15 | |
| 1356 | 13 | c.4066_4068delTT, |
| 1412 | 9 | L1412F, |
| 1408 | 5 | G1408R, G1408R, |
| 735 | 10 | A735V, A735T, A735E, |
| 732 | 14 | |
| 1360 | 14 | F1360C, |
| 734 | 14 | c.2201dupT, M734V, |
| 1401 | 8 | |
| 1399 | 13 | |
| 1354 | 14 | |
| 1424 | 14 | I1424V, |
| 1748 | 13 | p.G1748del, G1748D, |
| 738 | 11 | |
| 1405 | 4 | V1405M, V1405L, V1405L, |
| 740 | 15 | p.N740del, |
| 1409 | 6 | Y1409X, Y1409C, |
| 1400 | 10 | V1400I, |
| 1343 | 14 | |
| 1345 | 11 | W1345C, W1345C, |
| 1717 | 14 | L1717P, |
| 1342 | 11 | |
| 1416 | 15 | A1416E, A1416G, c.4245+2T>A, c.4245+1G>C, c.4245+1G>A, |
| 736 | 11 | L736P, |
| 1750 | 13 | L1750F, |
| 1722 | 14 | N1722D, |
| 1749 | 10 | I1749N, |
| 1347 | 14 | |
| 1415 | 14 | |
| 1414 | 12 | Q1414H, Q1414H, |
| 1402 | 9 | |
| 1413 | 10 |