SCN5A Variant c.2582_2583delTT
Summary of observed carriers, functional annotations, and structural context for SCN5A c.2582_2583delTT. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
10%
1/21 effective observations
Estimated BrS1 penetrance
70%
14/21 effective observations
Total carriers
11
11 BrS1 · 0 LQT3 · 0 unaffected
Variant features alone are equivalent to phenotyping 3 individuals for Brugada syndrome and 1 individuals for LQT3.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
|---|---|---|---|---|---|
| NA | NA | NA | None | 51 | 39 |
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 |
|---|---|---|---|---|---|---|---|
| 19251209 | 2009 | 1 | 0 | 1 | 0 | ||
| 19029124 | 2009 | 1 | 0 | 1 | 0 | ||
| 21273195 | 2011 | 7 | 0 | 7 | 0 | ||
| 22885917 | 2012 | 3 | 0 | 3 | 0 | ||
| 26921764 | 2016 | 1 | 0 | 1 | 0 | ||
| 26941339 | 2016 | 2 | 0 | 2 | 0 | ||
| 20129283 | 2010 | 11 | 0 | 11 | 0 | ||
| 29759671 | 2018 | 1 | 0 | 1 | 0 | ||
| Literature, cohort, and gnomAD | – | 11 | 0 | 0 | 11 | – | |
| Variant features alone | – | 15 | 11 | 1 | 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.
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 | 11 | I891N, I891T, |
| 880 | 11 | |
| 888 | 15 | |
| 223 | 14 | V223L, |
| 856 | 8 | V856L, V856L, |
| 890 | 10 | I890T, |
| 901 | 15 | E901K, S901L, |
| 919 | 9 | |
| 862 | 5 | |
| 867 | 12 | E867K, E867Q, E867X, |
| 859 | 8 | |
| 894 | 14 | I894M, |
| 863 | 8 | |
| 904 | 14 | W904X, |
| 887 | 10 | |
| 864 | 7 | |
| 886 | 13 | H886P, H886Q, H886Q, |
| 216 | 11 | S216X, S216L, |
| 221 | 12 | |
| 909 | 9 | |
| 852 | 14 | |
| 854 | 10 | c.2559delT, |
| 876 | 14 | |
| 857 | 5 | G857D, |
| 868 | 13 | c.2602delC, L868X, |
| 902 | 10 | |
| 882 | 11 | |
| 881 | 6 | |
| 921 | 13 | |
| 922 | 13 | V922I |
| 860 | 4 | p.L860fsx89, |
| 911 | 10 | G911E, |
| 920 | 14 | |
| 889 | 15 | |
| 858 | 8 | M858L, M858L, |
| 217 | 12 | |
| 918 | 8 | |
| 855 | 10 | |
| 917 | 11 | L917V, L917R, |
| 865 | 7 | |
| 913 | 9 | |
| 916 | 11 | |
| 912 | 12 | Q912R, |
| 884 | 14 | |
| 906 | 6 | |
| 866 | 12 | S866P, S866L, |
| 910 | 6 | S910L, |
| 903 | 11 | p.M903CfsX29, |
| 853 | 11 | |
| 219 | 13 | p.R219HfsX11, R219C, c.656_657insATTCA, R219H, |
| 877 | 13 | |
| 879 | 15 | W879R, W879R, |
| 883 | 13 | |
| 905 | 11 | |
| 915 | 6 | C915R, |
| 215 | 13 | p.L215CfsX10, |
| 850 | 15 | V850M, c.2549_2550insTG, |
| 908 | 12 | |
| 914 | 7 | |
| 861 | 0 | p.F861WfsX90, c.2582_2583delTT, |
| 220 | 9 | T220I, |
| 907 | 10 |