SCN5A Variant L315P
Summary of observed carriers, functional annotations, and structural context for SCN5A L315P. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
0%
0/11 effective observations
Estimated BrS1 penetrance
56%
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 (%) |
|---|---|---|---|---|---|
| -2.95 | 0.484 | -2.09 | 0.714 | 74 | 0 |
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 |
|---|---|---|---|---|---|---|---|
| 20129283 | 2010 | 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) |
|---|---|---|---|---|---|---|
| 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 |
|---|---|---|
| 300 | 15 | V300I, |
| 301 | 14 | |
| 302 | 14 | |
| 303 | 13 | |
| 304 | 13 | |
| 305 | 12 | D305N, |
| 306 | 11 | L306F, L306V, |
| 307 | 11 | |
| 308 | 10 | |
| 309 | 9 | S309N, S309C, |
| 310 | 8 | D310N, |
| 311 | 8 | |
| 312 | 7 | E312K, c.934+4C>T, c.934+1G>A, |
| 313 | 5 | |
| 314 | 4 | |
| 315 | 0 | L315P, |
| 316 | 4 | |
| 317 | 5 | K317M, K317E, K317N, K317N, |
| 318 | 7 | |
| 319 | 8 | G319S, G319R, G319C, |
| 320 | 8 | T320N, |
| 321 | 9 | S321Y, |
| 322 | 10 | |
| 323 | 11 | |
| 324 | 11 | |
| 325 | 12 | L325R, |
| 326 | 13 | |
| 327 | 13 | |
| 328 | 14 | |
| 329 | 14 | |
| 330 | 15 | S330F, |