SCN5A Variant V240M
Summary of observed carriers, functional annotations, and structural context for SCN5A V240M. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
27%
3/19 effective observations
Estimated BrS1 penetrance
25%
4/19 effective observations
Total carriers
9
3 BrS1 · 2 LQT3 · 4 unaffected
Variant features alone are equivalent to phenotyping 1 individuals for Brugada syndrome and 1 individuals for LQT3.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
|---|---|---|---|---|---|
| -2.93 | 1 | 0.05 | 0.917 | 20 | 49 |
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 |
|---|---|---|---|---|---|---|---|
| 24349418 | 2013 | 1 | 1 | 0 | 0 | ||
| 19843921 | 2009 | 1 | 0 | 1 | 0 | ||
| 21273195 | 2011 | 3 | 0 | 3 | 0 | ||
| 19716085 | 2009 | 1 | 1 | 0 | 0 | ||
| 20129283 | 2010 | 1 | 0 | 1 | 0 | ||
| 30059973 | 2018 | 1 | 1 | 0 | 0 | ||
| Literature, cohort, and gnomAD | – | 9 | 4 | 2 | 3 | – | |
| Variant features alone | – | 15 | 13 | 1 | 1 | – | – |
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 |
|---|---|---|
| 848 | 11 | I848F, |
| 937 | 14 | |
| 839 | 14 | L839P, |
| 842 | 10 | |
| 249 | 14 | K249X, |
| 247 | 11 | V247L, V247L, |
| 240 | 0 | V240M, |
| 231 | 9 | c.692_693delCA, |
| 193 | 9 | W193R, W193R, W193X, |
| 418 | 13 | E418K, |
| 926 | 14 | |
| 237 | 6 | |
| 228 | 12 | K228R, |
| 925 | 12 | I925F, |
| 227 | 10 | L227P, |
| 234 | 12 | P234S, |
| 934 | 15 | |
| 933 | 10 | |
| 229 | 12 | |
| 246 | 10 | |
| 412 | 13 | V412D, |
| 196 | 14 | |
| 852 | 15 | |
| 245 | 9 | Q245K, |
| 845 | 8 | c.2533delG, |
| 232 | 12 | V232I, V232F, |
| 244 | 6 | |
| 415 | 11 | A415T, |
| 191 | 14 | |
| 849 | 11 | |
| 226 | 14 | A226G, A226V, |
| 420 | 12 | |
| 248 | 12 | |
| 241 | 4 | |
| 235 | 9 | c.703+1G>A, G235R, G235R, c.704-1G>C, |
| 840 | 13 | |
| 843 | 13 | T843A, |
| 419 | 9 | Q419X, |
| 930 | 11 | c.2787+17_2787+18insACACACACACACACACACACACA, c.2788-6C>T |
| 423 | 13 | |
| 837 | 14 | |
| 239 | 5 | I239V, I239V , |
| 230 | 7 | I230V, I230T, I230M, |
| 242 | 6 | A242D, |
| 929 | 11 | |
| 416 | 11 | Y416C, |
| 413 | 15 | A413T, A413E, |
| 841 | 10 | p.N841TfsX2, N841K, N841K, |
| 236 | 6 | |
| 847 | 14 | |
| 846 | 12 | L846R, |
| 192 | 12 | |
| 936 | 14 | |
| 238 | 7 | |
| 233 | 9 | |
| 838 | 12 | |
| 422 | 14 | |
| 844 | 12 | L844RfsX3, |
| 243 | 5 |