SCN5A Variant L844RfsX3
Summary of observed carriers, functional annotations, and structural context for SCN5A L844RfsX3. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
14%
0/11 effective observations
Estimated BrS1 penetrance
54%
5/11 effective observations
Total carriers
1
1 BrS1 · 0 LQT3 · 0 unaffected
Variant features alone are equivalent to phenotyping 4 individuals for Brugada syndrome and 0 individuals for LQT3.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
|---|---|---|---|---|---|
| NA | NA | NA | None | 73 | 19 |
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 |
|---|---|---|---|---|---|---|---|
| 29574140 | 2018 | 1 | 0 | 1 | 0 | ||
| Literature, cohort, and gnomAD | – | 1 | 0 | 0 | 1 | – | |
| Variant features alone | – | 15 | 11 | 0 | 4 | – | – |
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) |
|---|---|---|---|---|---|---|
| 29574140 | 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 |
|---|---|---|
| 888 | 14 | |
| 848 | 6 | I848F, |
| 937 | 14 | |
| 895 | 15 | L895F, |
| 839 | 9 | L839P, |
| 842 | 7 | |
| 240 | 12 | V240M, |
| 231 | 11 | c.692_693delCA, |
| 1455 | 12 | |
| 1452 | 14 | |
| 926 | 14 | |
| 237 | 14 | |
| 228 | 14 | K228R, |
| 138 | 14 | M138I, M138I, M138I, |
| 227 | 12 | L227P, |
| 836 | 11 | V836M, |
| 234 | 9 | P234S, |
| 1451 | 14 | V1451L, V1451D, |
| 142 | 12 | |
| 934 | 12 | |
| 933 | 13 | |
| 229 | 9 | |
| 851 | 11 | c.2550_2551dupGT, F851L, p.F851CfsX19, c.2552_2553dupGT, F851L, F851L, |
| 852 | 13 | |
| 845 | 5 | c.2533delG, |
| 232 | 9 | V232I, V232F, |
| 892 | 15 | F892I, |
| 849 | 10 | |
| 226 | 12 | A226G, A226V, |
| 235 | 11 | c.703+1G>A, G235R, G235R, c.704-1G>C, |
| 840 | 5 | |
| 843 | 5 | T843A, |
| 1456 | 14 | |
| 930 | 12 | c.2787+17_2787+18insACACACACACACACACACACACA, c.2788-6C>T, |
| 1459 | 14 | c.4376_4379delTCTT |
| 837 | 9 | |
| 239 | 10 | I239V, I239V , |
| 230 | 8 | I230V, I230T, I230M, |
| 242 | 15 | A242D, |
| 841 | 6 | p.N841TfsX2, N841K, N841K, |
| 236 | 10 | |
| 847 | 6 | |
| 846 | 7 | L846R, |
| 238 | 13 | |
| 233 | 6 | |
| 838 | 10 | |
| 141 | 15 | I141V, I141N, |
| 853 | 15 | |
| 844 | 0 | L844RfsX3, |
| 850 | 11 | V850M, c.2549_2550insTG, |
| 243 | 13 | |
| 835 | 13 | S835A, S835L, |
| 145 | 13 | |
| 931 | 14 |