SCN5A Variant L839P
Summary of observed carriers, functional annotations, and structural context for SCN5A L839P. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
7%
0/15 effective observations
Estimated BrS1 penetrance
56%
8/15 effective observations
Total carriers
5
4 BrS1 · 0 LQT3 · 1 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 (%) |
|---|---|---|---|---|---|
| -6.93 | 0.999 | -3.25 | 0.989 | 57 | 13 |
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 |
|---|---|---|---|---|---|---|---|
| 16426410 | 2006 | 5 | 0 | 4 | 0 | ||
| 16643399 | 2006 | 1 | 0 | 1 | 0 | ||
| 17404158 | 2007 | 1 | 0 | 1 | 0 | ||
| 20031634 | 2009 | 5 | 0 | 4 | 0 | ||
| 26921764 | 2016 | 1 | 0 | 1 | 0 | ||
| 20129283 | 2010 | 1 | 0 | 1 | 0 | ||
| 30059973 | 2018 | 1 | 1 | 0 | 0 | ||
| Literature, cohort, and gnomAD | – | 5 | 1 | 0 | 4 | – | |
| 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.
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 | 14 | I848F, |
| 939 | 13 | L939F, |
| 937 | 7 | |
| 839 | 0 | L839P, |
| 842 | 5 | |
| 1457 | 13 | |
| 240 | 14 | V240M, |
| 1455 | 10 | |
| 1452 | 14 | |
| 1461 | 13 | T1461S, T1461S, |
| 836 | 6 | V836M, |
| 234 | 11 | P234S, |
| 1451 | 15 | V1451L, V1451D, |
| 934 | 7 | |
| 1458 | 14 | S1458Y, |
| 933 | 10 | |
| 935 | 12 | L935P, |
| 1464 | 13 | c.4389_4396delCCTCTTTA, L1464P |
| 845 | 10 | c.2533delG, |
| 830 | 14 | |
| 833 | 9 | G833R, G833R, |
| 940 | 11 | S940N, |
| 849 | 15 | |
| 831 | 11 | |
| 420 | 14 | |
| 938 | 9 | |
| 235 | 12 | c.703+1G>A, G235R, G235R, c.704-1G>C, |
| 840 | 4 | |
| 942 | 11 | |
| 843 | 6 | T843A, |
| 1456 | 10 | |
| 930 | 11 | c.2787+17_2787+18insACACACACACACACACACACACA, c.2788-6C>T, |
| 1459 | 11 | c.4376_4379delTCTT, |
| 834 | 10 | N834D, |
| 1460 | 9 | F1460L, F1460L, F1460L, |
| 837 | 6 | |
| 239 | 10 | I239V, I239V , |
| 1454 | 14 | |
| 230 | 14 | I230V, I230T, I230M, |
| 242 | 15 | A242D, |
| 416 | 12 | Y416C, |
| 841 | 7 | p.N841TfsX2, N841K, N841K, |
| 236 | 13 | |
| 847 | 12 | |
| 941 | 10 | S941N, S941F, |
| 846 | 10 | L846R, |
| 936 | 11 | |
| 238 | 12 | |
| 233 | 11 | |
| 838 | 5 | |
| 844 | 9 | L844RfsX3, |
| 829 | 13 | |
| 243 | 15 | |
| 932 | 14 | |
| 832 | 8 | |
| 835 | 5 | S835A, S835L, |
| 828 | 13 | L828V, |
| 931 | 12 | |
| 1463 | 13 | N1463Y, |