SCN5A Variant R1027Q
Summary of observed carriers, functional annotations, and structural context for SCN5A R1027Q. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
9%
1/21 effective observations
Estimated BrS1 penetrance
3%
0/21 effective observations
Total carriers
11
0 BrS1 · 1 LQT3 · 10 unaffected
Variant features alone are equivalent to phenotyping 0 individuals for Brugada syndrome and 0 individuals for LQT3.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
|---|---|---|---|---|---|
| -0.92 | 0.999 | 0.31 | 0.383 | 0 | 4 |
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 |
|---|---|---|---|---|---|---|---|
| 25904541 | 2015 | 1 | 1 | 0 | 0 | ||
| Literature, cohort, and gnomAD | – | 11 | 10 | 1 | 0 | – | |
| Variant features alone | – | 15 | 15 | 0 | 0 | – | – |
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) |
|---|---|---|---|---|---|---|
| 25904541 | 2015 |
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 |
|---|---|---|
| 1012 | 15 | |
| 1013 | 14 | |
| 1014 | 14 | P1014S, |
| 1015 | 13 | E1015K, p.G1015DfsX14, |
| 1016 | 13 | T1016M, c.3045_3046delGA, |
| 1017 | 12 | |
| 1018 | 11 | K1018E, |
| 1019 | 11 | |
| 1020 | 10 | |
| 1021 | 9 | P1021S, |
| 1022 | 8 | |
| 1023 | 8 | R1023P, R1023H, R1023C, |
| 1024 | 7 | K1024R, |
| 1025 | 5 | E1025A, |
| 1026 | 4 | |
| 1027 | 0 | R1027P, R1027W, R1027Q, |
| 1028 | 4 | |
| 1029 | 5 | E1029K, |
| 1030 | 7 | |
| 1031 | 8 | p.G1031fsX27, |
| 1032 | 8 | E1032D, E1032D, E1032K, |
| 1033 | 9 | Q1033R, |
| 1034 | 10 | P1034T, |
| 1035 | 11 | G1035V, |
| 1036 | 11 | |
| 1037 | 12 | |
| 1038 | 13 | |
| 1039 | 13 | |
| 1040 | 14 | G1040R, G1040R, |
| 1041 | 14 | D1041N, D1041G, |
| 1042 | 15 |