SCN5A Variant G400R
Summary of observed carriers, functional annotations, and structural context for SCN5A G400R. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
6%
0/15 effective observations
Estimated BrS1 penetrance
34%
5/15 effective observations
Total carriers
5
3 BrS1 · 0 LQT3 · 2 unaffected
Variant features alone are equivalent to phenotyping 2 individuals for Brugada syndrome and 0 individuals for LQT3.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
|---|---|---|---|---|---|
| -7.85 | 1 | -6.27 | 0.965 | 19 | 13 |
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 |
|---|---|---|---|---|---|---|---|
| 27707468 | 2016 | 1 | 0 | 1 | 0 | ||
| 28146213 | 2017 | 4 | 0 | 2 | 0 | ||
| Literature, cohort, and gnomAD | – | 5 | 2 | 0 | 3 | – | |
| Variant features alone | – | 15 | 13 | 0 | 2 | – | – |
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 |
|---|---|---|
| 403 | 5 | |
| 364 | 13 | |
| 404 | 5 | L404V, L404Q, |
| 396 | 6 | V396A, V396L, |
| 1653 | 13 | |
| 391 | 14 | |
| 254 | 13 | |
| 372 | 14 | |
| 1771 | 11 | I1771T, |
| 401 | 4 | S401P, |
| 1634 | 15 | L1634P, |
| 1764 | 13 | c.5290delG, V1764F, |
| 371 | 9 | Q371E, |
| 409 | 14 | L409V, L409P, |
| 928 | 14 | L928P, |
| 1650 | 11 | L1650F, |
| 260 | 8 | |
| 366 | 11 | |
| 365 | 10 | |
| 258 | 12 | V258A, |
| 369 | 5 | M369K, |
| 1767 | 10 | Y1767C, |
| 1660 | 14 | I1660S, I1660V, |
| 1654 | 12 | |
| 402 | 6 | F402L, F402L, F402L |
| 1649 | 14 | A1649V, |
| 1768 | 12 | I1768V, |
| 267 | 13 | |
| 262 | 13 | S262G, |
| 256 | 10 | |
| 399 | 5 | |
| 397 | 6 | I397V, I397F, I397T, |
| 405 | 8 | |
| 1657 | 11 | |
| 362 | 14 | |
| 261 | 9 | |
| 1709 | 13 | T1709M, T1709R, p.T1709del, |
| 392 | 11 | |
| 255 | 15 | |
| 1772 | 15 | L1772V, |
| 395 | 8 | |
| 393 | 11 | |
| 394 | 10 | |
| 410 | 14 | A410V, |
| 1770 | 14 | I1770V, |
| 1658 | 13 | |
| 264 | 8 | |
| 1651 | 14 | |
| 1708 | 15 | T1708I, |
| 259 | 12 | |
| 265 | 13 | A265V, |
| 408 | 11 | |
| 374 | 13 | W374G, |
| 253 | 12 | |
| 1705 | 14 | |
| 407 | 10 | |
| 367 | 13 | R367C, R367L, R367H, |
| 263 | 11 | V263I, |
| 370 | 10 | T370M, |
| 1661 | 14 | G1661R, G1661R, G1661E, |
| 1631 | 15 | G1631D, |
| 406 | 9 | N406K, N406S, N406K, |
| 368 | 9 | |
| 398 | 7 | |
| 1647 | 13 | |
| 257 | 9 | |
| 400 | 0 | G400R, G400E, G400A, G400R, |
| 1646 | 14 | |
| 1664 | 15 |