SCN5A Variant p.L729del
Summary of observed carriers, functional annotations, and structural context for SCN5A p.L729del. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
7%
0/11 effective observations
Estimated BrS1 penetrance
48%
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 (%) |
|---|---|---|---|---|---|
| NA | NA | NA | None | 62 | 7 |
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 |
|---|---|---|---|---|---|---|---|
| 28069705 | 2017 | 1 | 0 | 0 | 1 | ARVD | |
| 22885917 | 2012 | 1 | 0 | 1 | 0 | ||
| 30059973 | 2018 | 1 | 1 | 0 | 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.
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 | 10 | I723V, |
| 758 | 14 | G758E, |
| 811 | 13 | R811G, R811H, c.2435_2436+3delTGGTAinsCGCCT, |
| 733 | 6 | F733L, |
| 745 | 14 | |
| 821 | 14 | |
| 760 | 11 | p.F760SfsX5, |
| 721 | 12 | |
| 812 | 14 | L812Q, |
| 1350 | 14 | I1350L, I1350T, |
| 759 | 11 | I759V, c.2274delG, p.I759FfsX6, |
| 755 | 11 | |
| 731 | 7 | T731I, |
| 754 | 14 | |
| 726 | 5 | |
| 818 | 12 | |
| 737 | 14 | |
| 720 | 15 | |
| 750 | 15 | Q750R, |
| 822 | 15 | W822C, W822X, |
| 749 | 11 | |
| 1346 | 14 | L1346I, L1346P, |
| 724 | 9 | T724I, |
| 728 | 4 | V728I, |
| 727 | 7 | |
| 735 | 10 | A735V, A735E, A735T, |
| 732 | 5 | |
| 734 | 10 | c.2201dupT, M734V, |
| 756 | 7 | |
| 814 | 11 | R814Q, |
| 722 | 10 | |
| 757 | 13 | |
| 817 | 13 | K817E, |
| 752 | 9 | G752R, |
| 815 | 12 | |
| 725 | 7 | |
| 751 | 12 | V751I, V751F, |
| 736 | 12 | L736P, |
| 730 | 6 | N730K, |
| 753 | 11 | |
| 729 | 0 | p.L729del, |
| 748 | 11 | M748I, |