SCN5A Variant A242D
Summary of observed carriers, functional annotations, and structural context for SCN5A A242D. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
67%
4/11 effective observations
Estimated BrS1 penetrance
11%
1/11 effective observations
Total carriers
1
0 BrS1 · 1 LQT3 · 0 unaffected
Variant features alone are equivalent to phenotyping 1 individuals for Brugada syndrome and 3 individuals for LQT3.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
|---|---|---|---|---|---|
| -5.86 | 1 | -4.24 | 0.975 | 4 | 84 |
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 |
|---|---|---|---|---|---|---|---|
| 30059973 | 2018 | 1 | 1 | 0 | 0 | ||
| Literature, cohort, and gnomAD | – | 1 | 0 | 1 | 0 | – | |
| Variant features alone | – | 15 | 11 | 3 | 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.
| PubMed ID | Year | Cell Type | Peak Current (% WT) | V1/2 Activation (mV) | V1/2 Inactivation (mV) | Late/Persistent Current (% WT) |
|---|---|---|---|---|---|---|
| 30059973 | 2018 |
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 | 10 | M414V, |
| 939 | 15 | L939F, |
| 937 | 11 | |
| 839 | 15 | L839P, |
| 842 | 10 | |
| 249 | 9 | K249X, |
| 247 | 8 | V247L, V247L, |
| 240 | 6 | V240M, |
| 231 | 15 | c.692_693delCA, |
| 193 | 14 | W193R, W193R, W193X, |
| 418 | 9 | E418K, |
| 926 | 13 | |
| 250 | 12 | |
| 409 | 13 | L409V, L409P, |
| 237 | 9 | |
| 928 | 13 | L928P, |
| 925 | 12 | I925F, |
| 417 | 10 | |
| 934 | 13 | |
| 933 | 7 | |
| 246 | 5 | |
| 935 | 13 | L935P, |
| 412 | 8 | V412D, |
| 924 | 14 | V924I, |
| 927 | 15 | N927S, N927K, N927K, |
| 245 | 6 | Q245K, |
| 845 | 11 | c.2533delG, |
| 244 | 6 | |
| 415 | 6 | A415T, |
| 940 | 13 | S940N |
| 849 | 14 | |
| 420 | 9 | |
| 248 | 10 | |
| 241 | 3 | |
| 235 | 11 | c.703+1G>A, G235R, G235R, c.704-1G>C, |
| 840 | 15 | |
| 843 | 14 | T843A, |
| 419 | 6 | Q419X, |
| 930 | 10 | c.2787+17_2787+18insACACACACACACACACACACACA, c.2788-6C>T, |
| 423 | 12 | |
| 239 | 5 | I239V, I239V , |
| 230 | 12 | I230V, I230T, I230M, |
| 251 | 15 | |
| 410 | 13 | A410V, |
| 242 | 0 | A242D, |
| 929 | 9 | |
| 416 | 6 | Y416C, |
| 413 | 9 | A413T, A413E, |
| 841 | 12 | p.N841TfsX2, N841K, N841K, |
| 236 | 10 | |
| 408 | 13 | |
| 846 | 14 | L846R, |
| 936 | 10 | |
| 238 | 7 | |
| 233 | 14 | |
| 838 | 12 | |
| 422 | 11 | |
| 421 | 13 | |
| 844 | 15 | L844RfsX3, |
| 411 | 10 | V411M, |
| 243 | 4 | |
| 932 | 12 | |
| 931 | 13 |