SCN5A Variant E1053K
Summary of observed carriers, functional annotations, and structural context for SCN5A E1053K. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
5%
2/50 effective observations
Estimated BrS1 penetrance
13%
6/50 effective observations
Total carriers
40
5 BrS1 · 2 LQT3 · 33 unaffected
Variant features alone are equivalent to phenotyping 1 individuals for Brugada syndrome and 0 individuals for LQT3.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
|---|---|---|---|---|---|
| -3.73 | 0.999 | -0.22 | 0.872 | 15 | 2 |
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 | ||
| 19026623 | 2009 | 1 | 1 | 0 | 0 | ||
| 23321620 | 2013 | 1 | 0 | 1 | 0 | ||
| 26746457 | 2016 | 1 | 0 | 0 | 0 | ||
| 28391114 | 2017 | 5 | 0 | 0 | 1 | SUDS | |
| 19716085 | 2009 | 1 | 1 | 0 | 0 | ||
| 20129283 | 2010 | 3 | 0 | 3 | 0 | ||
| 29579189 | 2018 | 1 | 0 | 0 | 1 | Afib | |
| 30059973 | 2018 | 1 | 1 | 0 | 0 | ||
| Literature, cohort, and gnomAD | – | 40 | 33 | 2 | 5 | – | |
| Variant features alone | – | 15 | 14 | 0 | 1 | – | – |
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) |
|---|---|---|---|---|---|---|
| 19026623 | 2009 | |||||
| 23321620 | 2013 | |||||
| 26746457 | 2016 | |||||
| 28391114 | 2017 | |||||
| 19716085 | 2009 | |||||
| 15579534 | 2004 | HEK | 100 | -8.3 | -4.7 | |
| 20129283 | 2010 | |||||
| 24573164 | 2014 | HEK | 75 | 3.71 | ||
| 29579189 | 2018 | |||||
| 30059973 | 2018 | |||||
| 11076825 | 2000 | |||||
| 11901046 | 2002 |
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 |
|---|---|---|
| 1038 | 15 | |
| 1039 | 14 | |
| 1040 | 14 | G1040R, G1040R, |
| 1041 | 13 | D1041G, D1041N, |
| 1042 | 13 | |
| 1043 | 12 | E1043K, |
| 1044 | 11 | |
| 1045 | 11 | V1045M, |
| 1046 | 10 | |
| 1047 | 9 | c.3140_3141dupTG, |
| 1048 | 8 | p.P1048SfsX96, c.3142_3143insTG, P1048S, |
| 1049 | 8 | |
| 1050 | 7 | p.A1050CfsX9, A1050T, p.A1050DfsX9, |
| 1051 | 5 | V1051A, |
| 1052 | 4 | A1052D, p.A1052CfsX7 |
| 1053 | 0 | E1053K, |
| 1054 | 4 | |
| 1055 | 5 | D1055G, |
| 1056 | 7 | T1056A, |
| 1057 | 8 | |
| 1058 | 8 | c.3171_3172delTGinsA, |
| 1059 | 9 | Q1059X, |
| 1060 | 10 | |
| 1061 | 11 | E1061D, E1061D, |
| 1062 | 11 | D1062H, |
| 1063 | 12 | E1063G, |
| 1064 | 13 | p.E1064del, |
| 1065 | 13 | |
| 1066 | 14 | S1066G, |
| 1067 | 14 | L1067R, |
| 1068 | 15 | G1068A, G1068D, |