SCN5A Variant G758E
Summary of observed carriers, functional annotations, and structural context for SCN5A G758E. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
9%
0/11 effective observations
Estimated BrS1 penetrance
50%
5/11 effective observations
Total carriers
1
1 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 (%) |
|---|---|---|---|---|---|
| -6.43 | 0.521 | -3.3 | 0.947 | 63 | 13 |
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 | – | 1 | 0 | 0 | 1 | – | |
| 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.
| 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 |
|---|---|---|
| 719 | 14 | |
| 723 | 11 | I723V, |
| 766 | 11 | |
| 758 | 0 | G758E, |
| 811 | 13 | R811H, c.2435_2436+3delTGGTAinsCGCCT, R811G, |
| 733 | 14 | F733L, |
| 760 | 6 | p.F760SfsX5, |
| 765 | 10 | |
| 759 | 4 | p.I759FfsX6, c.2274delG, I759V, |
| 792 | 9 | |
| 764 | 10 | M764K, M764R, |
| 755 | 6 | |
| 791 | 14 | L791F, |
| 800 | 14 | R800C, R800L, R800H, |
| 754 | 7 | |
| 726 | 10 | |
| 797 | 15 | G797V, |
| 750 | 13 | Q750R, |
| 788 | 11 | I788V, |
| 793 | 9 | L793F, |
| 762 | 6 | |
| 727 | 13 | |
| 767 | 13 | |
| 756 | 7 | |
| 814 | 11 | R814Q, |
| 722 | 13 | |
| 757 | 4 | |
| 768 | 14 | |
| 786 | 13 | |
| 817 | 15 | K817E, |
| 761 | 4 | |
| 752 | 10 | G752R, |
| 790 | 13 | |
| 763 | 8 | E763D, E763K, |
| 751 | 11 | V751I, V751F, |
| 796 | 11 | |
| 785 | 13 | D785N, |
| 730 | 12 | N730K, |
| 789 | 9 | V789A, V789I, |
| 753 | 9 | |
| 729 | 14 | p.L729del, |
| 795 | 13 | |
| 794 | 14 |