SCN5A Variant H886P
Summary of observed carriers, functional annotations, and structural context for SCN5A H886P. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
6%
0/12 effective observations
Estimated BrS1 penetrance
41%
4/12 effective observations
Total carriers
2
1 BrS1 · 0 LQT3 · 1 unaffected
Variant features alone are equivalent to phenotyping 3 individuals for Brugada syndrome and 0 individuals for LQT3.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
|---|---|---|---|---|---|
| -9.27 | 0.993 | -2.62 | 0.979 | 53 | 0 |
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 |
|---|---|---|---|---|---|---|---|
| 20129283 | 2010 | 1 | 0 | 1 | 0 | ||
| Literature, cohort, and gnomAD | – | 2 | 1 | 0 | 1 | – | |
| Variant features alone | – | 15 | 12 | 0 | 3 | – | – |
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) |
|---|---|---|---|---|---|---|
| 20129283 | 2010 |
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 |
|---|---|---|
| 891 | 10 | I891N, I891T, |
| 880 | 5 | |
| 888 | 8 | |
| 856 | 14 | V856L, V856L, |
| 890 | 7 | I890T, |
| 901 | 14 | E901K, S901L, |
| 919 | 15 | |
| 862 | 11 | |
| 859 | 15 | |
| 1430 | 13 | D1430N, |
| 1426 | 11 | |
| 1445 | 12 | Y1445H, |
| 894 | 13 | I894M, |
| 1447 | 9 | |
| 1444 | 7 | L1444I, |
| 153 | 14 | |
| 1440 | 9 | W1440X, |
| 149 | 13 | |
| 1429 | 11 | |
| 1442 | 13 | Y1442N, Y1442C, |
| 1450 | 14 | |
| 887 | 5 | |
| 1451 | 14 | V1451L, V1451D |
| 864 | 15 | |
| 886 | 0 | H886P, H886Q, H886Q, |
| 851 | 14 | c.2550_2551dupGT, F851L, p.F851CfsX19, c.2552_2553dupGT, F851L, F851L, |
| 1423 | 15 | D1423H, |
| 854 | 10 | c.2559delT, |
| 876 | 10 | |
| 1422 | 12 | M1422R, |
| 857 | 11 | G857D, |
| 902 | 12 | |
| 882 | 8 | |
| 892 | 11 | F892I, |
| 881 | 7 | |
| 893 | 11 | R893C, R893H, |
| 889 | 6 | |
| 858 | 10 | M858L, M858L, |
| 855 | 12 | |
| 1425 | 11 | |
| 865 | 10 | |
| 1427 | 14 | A1427S, A1427E, |
| 1446 | 13 | |
| 1448 | 13 | I1448L, I1448T, |
| 884 | 8 | |
| 906 | 14 | |
| 866 | 14 | S866P, S866L, |
| 878 | 9 | R878C, R878H, R878L, |
| 1421 | 14 | |
| 885 | 6 | |
| 1443 | 13 | N1443S, |
| 1441 | 9 | E1441Q, |
| 152 | 11 | D152N, |
| 853 | 15 | |
| 877 | 9 | |
| 151 | 15 | |
| 879 | 6 | W879R, W879R, |
| 883 | 5 | |
| 905 | 13 | |
| 875 | 14 | |
| 1428 | 14 | A1428S, A1428V, |
| 850 | 14 | V850M, c.2549_2550insTG, |
| 861 | 13 | p.F861WfsX90, c.2582_2583delTT, |