SCN5A Variant V789I
Summary of observed carriers, functional annotations, and structural context for SCN5A V789I. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
0%
0/25 effective observations
Estimated BrS1 penetrance
7%
1/25 effective observations
Total carriers
15
1 BrS1 · 0 LQT3 · 14 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 (%) |
|---|---|---|---|---|---|
| -0.99 | 0.982 | 1.79 | 0.896 | 5 | 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 |
|---|---|---|---|---|---|---|---|
| 20129283 | 2010 | 1 | 0 | 1 | 0 | ||
| Literature, cohort, and gnomAD | – | 15 | 14 | 0 | 1 | – | |
| 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) |
|---|---|---|---|---|---|---|
| 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 |
|---|---|---|
| 723 | 13 | I723V, |
| 766 | 13 | |
| 758 | 9 | G758E, |
| 811 | 11 | R811G, R811H, c.2435_2436+3delTGGTAinsCGCCT, |
| 808 | 15 | R808C, R808H, R808P, |
| 769 | 15 | |
| 773 | 15 | P773S, |
| 760 | 7 | p.F760SfsX5, |
| 780 | 14 | |
| 776 | 12 | p.Y776del, |
| 765 | 9 | |
| 812 | 14 | L812Q, |
| 759 | 10 | I759V, c.2274delG, p.I759FfsX6, |
| 792 | 5 | |
| 764 | 7 | M764K, M764R, |
| 755 | 13 | |
| 777 | 12 | F777L, |
| 791 | 7 | L791F, |
| 754 | 13 | |
| 726 | 14 | |
| 797 | 13 | G797V, |
| 781 | 14 | W781X, |
| 788 | 5 | I788V, |
| 798 | 14 | |
| 782 | 11 | N782T, |
| 793 | 6 | L793F, |
| 762 | 9 | |
| 810 | 11 | |
| 727 | 13 | |
| 767 | 12 | |
| 756 | 12 | |
| 814 | 8 | R814Q, |
| 807 | 12 | |
| 816 | 14 | F816Y, F816L, |
| 813 | 10 | c.2437-5C>A, c.2436+12G>A, |
| 757 | 7 | |
| 768 | 11 | |
| 786 | 5 | |
| 817 | 12 | K817E, |
| 761 | 6 | |
| 752 | 15 | G752R, |
| 809 | 14 | |
| 815 | 14 | |
| 790 | 5 | |
| 784 | 9 | F784L, |
| 763 | 10 | E763D, E763K |
| 796 | 10 | |
| 785 | 7 | D785N, |
| 783 | 11 | I783T, |
| 730 | 13 | N730K, |
| 789 | 0 | V789A, V789I, |
| 753 | 13 | |
| 795 | 11 | |
| 787 | 7 | |
| 794 | 9 |