SCN5A Variant F892I
Summary of observed carriers, functional annotations, and structural context for SCN5A F892I. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
2%
0/12 effective observations
Estimated BrS1 penetrance
54%
6/12 effective observations
Total carriers
2
2 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 (%) |
|---|---|---|---|---|---|
| -5.74 | 0.906 | -3.65 | 0.982 | 59 | 1 |
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 |
|---|---|---|---|---|---|---|---|
| 11076825 | 2000 | 1 | 0 | 1 | 0 | ||
| 11901046 | 2002 | 1 | 0 | 1 | 0 | ||
| 22840528 | 2012 | 1 | 0 | 1 | 0 | ||
| 24721456 | 2014 | 2 | 0 | 2 | 0 | ||
| 30059973 | 2018 | 1 | 1 | 0 | 0 | ||
| Literature, cohort, and gnomAD | – | 2 | 0 | 0 | 2 | – | |
| 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 |
|---|---|---|
| 891 | 6 | I891N, I891T, |
| 880 | 14 | |
| 888 | 6 | |
| 848 | 13 | I848F, |
| 890 | 8 | I890T, |
| 901 | 14 | E901K, S901L, |
| 919 | 13 | |
| 896 | 6 | C896S, C896S, |
| 895 | 5 | L895F, |
| 1417 | 14 | |
| 842 | 15 | |
| 894 | 7 | I894M, |
| 1457 | 13 | |
| 1453 | 12 | |
| 1455 | 9 | |
| 1447 | 9 | |
| 1444 | 13 | L1444I, |
| 372 | 15 | |
| 1449 | 13 | Y1449S, Y1449C, |
| 1452 | 11 | |
| 926 | 10 | |
| 1429 | 15 | |
| 1450 | 10 | |
| 925 | 14 | I925F, |
| 887 | 9 | |
| 1451 | 7 | V1451L, V1451D, |
| 934 | 14 | |
| 886 | 11 | H886P, H886Q, H886Q, |
| 1458 | 11 | S1458Y, |
| 851 | 12 | c.2550_2551dupGT, F851L, p.F851CfsX19, c.2552_2553dupGT, F851L, F851L, |
| 897 | 9 | G897R, G897R, G897E, |
| 927 | 11 | N927S, N927K, N927K, |
| 852 | 14 | |
| 854 | 11 | c.2559delT, |
| 845 | 14 | c.2533delG, |
| 1422 | 10 | M1422R, |
| 857 | 14 | G857D, |
| 1418 | 9 | |
| 902 | 12 | |
| 892 | 0 | F892I, |
| 881 | 14 | |
| 849 | 12 | |
| 898 | 9 | |
| 893 | 7 | R893C, R893H, |
| 922 | 10 | V922I, |
| 889 | 6 | |
| 1420 | 14 | G1420R, G1420D, G1420V, G1420P, |
| 843 | 12 | T843A, |
| 1456 | 13 | |
| 930 | 13 | c.2787+17_2787+18insACACACACACACACACACACACA, c.2788-6C>T, |
| 1459 | 9 | c.4376_4379delTCTT |
| 855 | 14 | |
| 1425 | 10 | |
| 1454 | 8 | |
| 1446 | 15 | |
| 1424 | 14 | I1424V, |
| 1448 | 10 | I1448L, I1448T, |
| 884 | 12 | |
| 878 | 15 | R878C, R878H, R878L, |
| 1421 | 9 | |
| 885 | 11 | |
| 847 | 10 | |
| 846 | 9 | L846R, |
| 1416 | 12 | c.4245+1G>A, c.4245+1G>C, c.4245+2T>A, A1416E, A1416G, |
| 853 | 11 | |
| 879 | 11 | W879R, W879R, |
| 923 | 11 | |
| 883 | 14 | |
| 899 | 13 | |
| 1415 | 11 | |
| 844 | 15 | L844RfsX3, |
| 850 | 8 | V850M, c.2549_2550insTG, |
| 1419 | 14 | K1419E, |
| 931 | 11 |