SCN5A Variant p.N841TfsX2
Summary of observed carriers, functional annotations, and structural context for SCN5A p.N841TfsX2. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
63%
3/11 effective observations
Estimated BrS1 penetrance
12%
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 2 individuals for LQT3.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
|---|---|---|---|---|---|
| NA | NA | NA | None | 11 | 75 |
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 | 12 | 2 | 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 |
|---|---|---|
| 848 | 11 | I848F, |
| 937 | 10 | |
| 839 | 7 | L839P, |
| 842 | 6 | |
| 240 | 10 | V240M, |
| 231 | 11 | c.692_693delCA, |
| 1455 | 14 | |
| 237 | 11 | |
| 227 | 14 | L227P, |
| 836 | 8 | V836M, |
| 234 | 6 | P234S, |
| 934 | 11 | |
| 933 | 11 | |
| 229 | 11 | |
| 845 | 7 | c.2533delG, |
| 232 | 10 | V232F, V232I, |
| 833 | 13 | G833R, G833R, |
| 940 | 14 | S940N, |
| 849 | 13 | |
| 420 | 13 | |
| 938 | 14 | |
| 241 | 12 | |
| 235 | 6 | G235R, G235R, c.704-1G>C, c.703+1G>A, |
| 840 | 4 | |
| 843 | 7 | T843A, |
| 419 | 13 | Q419X, |
| 930 | 12 | c.2787+17_2787+18insACACACACACACACACACACACA, c.2788-6C>T, |
| 423 | 14 | |
| 834 | 13 | N834D, |
| 837 | 5 | |
| 239 | 7 | I239V , I239V, |
| 230 | 9 | I230V, I230M, I230T, |
| 242 | 12 | A242D, |
| 416 | 12 | Y416C, |
| 841 | 0 | N841K, p.N841TfsX2, N841K, |
| 236 | 7 | |
| 847 | 11 | |
| 941 | 14 | S941N, S941F, |
| 846 | 10 | L846R, |
| 936 | 14 | |
| 238 | 8 | |
| 233 | 5 | |
| 838 | 5 | |
| 844 | 6 | L844RfsX3, |
| 243 | 12 | |
| 832 | 14 | |
| 835 | 9 | S835A, S835L, |
| 931 | 15 |