SCN5A Variant V258A
Summary of observed carriers, functional annotations, and structural context for SCN5A V258A. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
71%
4/11 effective observations
Estimated BrS1 penetrance
8%
0/11 effective observations
Total carriers
1
0 BrS1 · 1 LQT3 · 0 unaffected
Variant features alone are equivalent to phenotyping 0 individuals for Brugada syndrome and 3 individuals for LQT3.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
|---|---|---|---|---|---|
| -3.83 | 0.999 | -0.85 | 0.937 | 0 | 91 |
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 |
|---|---|---|---|---|---|---|---|
| 27871843 | 2017 | 1 | 1 | 0 | 0 | ||
| Literature, cohort, and gnomAD | – | 1 | 0 | 1 | 0 | – | |
| Variant features alone | – | 15 | 12 | 3 | 0 | – | – |
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) |
|---|---|---|---|---|---|---|
| 27871843 | 2017 |
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 |
|---|---|---|
| 364 | 14 | |
| 266 | 12 | L266H, |
| 363 | 13 | |
| 1643 | 12 | I1643L |
| 404 | 11 | L404V, L404Q, |
| 396 | 14 | V396L, V396A, |
| 254 | 7 | |
| 401 | 14 | S401P, |
| 1634 | 14 | L1634P, |
| 1543 | 14 | V1543L, V1543L, V1543A, |
| 250 | 12 | |
| 1542 | 12 | |
| 928 | 15 | L928P, |
| 361 | 13 | |
| 260 | 6 | |
| 366 | 10 | |
| 365 | 11 | |
| 258 | 0 | V258A, |
| 924 | 14 | V924I, |
| 1546 | 12 | M1546T, |
| 369 | 11 | M369K, |
| 1630 | 13 | I1630V, I1630R, |
| 267 | 14 | |
| 262 | 6 | S262G, |
| 256 | 7 | |
| 405 | 14 | |
| 362 | 8 | |
| 261 | 5 | |
| 920 | 13 | |
| 1539 | 13 | C1539Y, C1539F, |
| 255 | 6 | |
| 917 | 15 | L917V, L917R, |
| 251 | 11 | |
| 264 | 11 | |
| 259 | 6 | |
| 1633 | 13 | |
| 265 | 10 | A265V, |
| 1637 | 15 | |
| 408 | 14 | |
| 253 | 9 | |
| 407 | 13 | |
| 358 | 11 | |
| 263 | 9 | V263I, |
| 359 | 13 | A359T, p.A359PfsX12, |
| 370 | 14 | T370M, |
| 1631 | 14 | G1631D, |
| 368 | 14 | |
| 252 | 11 | |
| 1647 | 14 | |
| 257 | 4 | |
| 400 | 12 | G400R, G400R, G400E, G400A, |
| 1646 | 15 |