SCN5A Variant V728I
Summary of observed carriers, functional annotations, and structural context for SCN5A V728I. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
3%
0/14 effective observations
Estimated BrS1 penetrance
23%
3/14 effective observations
Total carriers
4
1 BrS1 · 0 LQT3 · 3 unaffected
Variant features alone are equivalent to phenotyping 2 individuals for Brugada syndrome and 0 individuals for LQT3.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
|---|---|---|---|---|---|
| -0.95 | 0.083 | 2.71 | 0.638 | 35 | 5 |
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 |
|---|---|---|---|---|---|---|---|
| 22984773 | 2013 | 1 | 0 | 1 | 0 | ||
| Literature, cohort, and gnomAD | – | 4 | 3 | 0 | 1 | – | |
| Variant features alone | – | 15 | 13 | 0 | 2 | – | – |
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) |
|---|---|---|---|---|---|---|
| 22984773 | 2013 |
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 | 15 | |
| 723 | 10 | I723V, |
| 811 | 14 | R811G, R811H, c.2435_2436+3delTGGTAinsCGCCT, |
| 733 | 9 | F733L, |
| 821 | 10 | |
| 1339 | 14 | L1339F, p.L1339del, |
| 760 | 12 | p.F760SfsX5, |
| 721 | 11 | |
| 812 | 13 | L812Q, |
| 1350 | 14 | I1350L, I1350T, |
| 759 | 13 | I759V, c.2274delG, p.I759FfsX6, |
| 755 | 14 | |
| 731 | 5 | T731I, |
| 819 | 13 | |
| 726 | 6 | |
| 818 | 8 | |
| 825 | 15 | |
| 720 | 13 | |
| 822 | 11 | W822C, W822X, |
| 749 | 14 | |
| 1346 | 12 | L1346I, L1346P, |
| 724 | 6 | T724I, |
| 728 | 0 | V728I, |
| 820 | 14 | |
| 727 | 5 | |
| 735 | 10 | A735V, A735E, A735T, |
| 732 | 6 | |
| 734 | 10 | c.2201dupT, M734V, |
| 756 | 10 | |
| 814 | 10 | R814Q, |
| 816 | 13 | F816Y, F816L, |
| 722 | 10 | |
| 813 | 15 | c.2437-5C>A, c.2436+12G>A, |
| 757 | 14 | |
| 817 | 11 | K817E, |
| 752 | 13 | G752R, |
| 815 | 9 | |
| 1343 | 12 | |
| 1342 | 14 | |
| 725 | 6 | |
| 736 | 14 | L736P, |
| 730 | 7 | N730K, |
| 753 | 13 | |
| 1347 | 14 | |
| 729 | 4 | p.L729del, |