SCN5A Variant V247L
Summary of observed carriers, functional annotations, and structural context for SCN5A V247L. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
8%
1/27 effective observations
Estimated BrS1 penetrance
2%
0/27 effective observations
Total carriers
17
0 BrS1 · 1 LQT3 · 16 unaffected
Variant features alone are equivalent to phenotyping 0 individuals for Brugada syndrome and 0 individuals for LQT3.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
|---|---|---|---|---|---|
| -2.93 | 0.997 | 3.29 | 0.895 | 1 | 16 |
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 |
|---|---|---|---|---|---|---|---|
| 19716085 | 2009 | 1 | 1 | 0 | 0 | ||
| Literature, cohort, and gnomAD | – | 17 | 16 | 1 | 0 | – | |
| Variant features alone | – | 15 | 15 | 0 | 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) |
|---|---|---|---|---|---|---|
| 19716085 | 2009 |
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 |
|---|---|---|
| 414 | 12 | M414V, |
| 404 | 15 | L404V, L404Q, |
| 249 | 7 | K249X, |
| 247 | 0 | V247L, |
| 240 | 11 | V240M, |
| 254 | 9 | |
| 193 | 15 | W193R, W193X, |
| 418 | 14 | E418K, |
| 926 | 11 | |
| 250 | 5 | |
| 409 | 13 | L409P, L409V, |
| 928 | 10 | L928P, |
| 925 | 8 | I925F, |
| 933 | 11 | |
| 246 | 4 | |
| 412 | 9 | V412D, |
| 924 | 9 | V924I, |
| 927 | 13 | N927K, N927S, |
| 245 | 7 | Q245K, |
| 845 | 15 | c.2533delG, |
| 244 | 6 | |
| 415 | 10 | A415T, |
| 849 | 14 | |
| 921 | 11 | |
| 922 | 14 | V922I, |
| 405 | 14 | |
| 248 | 5 | |
| 241 | 9 | |
| 920 | 14 | |
| 419 | 14 | Q419X, |
| 930 | 11 | c.2788-6C>T, c.2787+17_2787+18insACACACACACACACACACACACA, |
| 255 | 13 | |
| 239 | 13 | I239V , I239V, |
| 251 | 7 | |
| 410 | 12 | A410V, |
| 242 | 8 | A242D, |
| 929 | 7 | |
| 416 | 13 | Y416C, |
| 413 | 13 | A413T, A413E, |
| 408 | 10 | |
| 253 | 10 | |
| 407 | 13 | |
| 192 | 15 | |
| 1642 | 15 | G1642E, |
| 923 | 14 | |
| 252 | 11 | |
| 411 | 9 | V411M, |
| 243 | 7 | |
| 932 | 12 | |
| 257 | 14 | |
| 931 | 14 |