SCN5A Variant c.2435_2436+3delTGGTAinsCGCCT
Summary of observed carriers, functional annotations, and structural context for SCN5A c.2435_2436+3delTGGTAinsCGCCT. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
7%
0/11 effective observations
Estimated BrS1 penetrance
39%
4/11 effective observations
Total carriers
1
1 BrS1 · 0 LQT3 · 0 unaffected
Variant features alone are equivalent to phenotyping 3 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 | 44 | 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 |
|---|---|---|---|---|---|---|---|
| 20129283 | 2010 | 1 | 0 | 1 | 0 | ||
| Literature, cohort, and gnomAD | – | 1 | 0 | 0 | 1 | – | |
| Variant features alone | – | 15 | 12 | 0 | 3 | – | – |
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 |
|---|---|---|
| 758 | 13 | G758E, |
| 1355 | 13 | |
| 811 | 0 | R811G, R811H, c.2435_2436+3delTGGTAinsCGCCT, |
| 733 | 10 | F733L, |
| 741 | 15 | p.M741_T742delinsI , |
| 808 | 5 | R808P, R808H, R808C, |
| 1352 | 13 | |
| 746 | 15 | E746K, |
| 1351 | 11 | M1351V, M1351R, |
| 760 | 11 | p.F760SfsX5, |
| 812 | 7 | L812Q, |
| 1350 | 9 | I1350T, I1350L, |
| 759 | 14 | c.2274delG, p.I759FfsX6, I759V, |
| 792 | 7 | |
| 755 | 13 | |
| 791 | 9 | L791F, |
| 731 | 10 | T731I, |
| 806 | 10 | V806M, |
| 800 | 14 | R800L, R800H, R800C, |
| 754 | 11 | |
| 726 | 14 | |
| 818 | 15 | |
| 1353 | 12 | V1353M, |
| 797 | 12 | G797V, |
| 737 | 10 | |
| 1348 | 14 | F1348L, |
| 750 | 10 | Q750R, |
| 1349 | 13 | |
| 749 | 10 | |
| 788 | 9 | I788V, |
| 1346 | 14 | L1346I, L1346P, |
| 805 | 10 | S805L, |
| 798 | 12 | |
| 793 | 11 | L793F, |
| 728 | 14 | V728I, |
| 810 | 7 | |
| 727 | 12 | |
| 735 | 12 | A735V, A735E, A735T, |
| 732 | 13 | |
| 734 | 6 | c.2201dupT, M734V, |
| 756 | 11 | |
| 814 | 6 | R814Q, |
| 807 | 8 | |
| 816 | 13 | F816L, F816Y, |
| 813 | 8 | c.2436+12G>A, c.2437-5C>A, |
| 757 | 9 | |
| 786 | 15 | |
| 1354 | 9 | |
| 817 | 14 | K817E, |
| 761 | 14 | |
| 752 | 10 | G752R, |
| 809 | 6 | |
| 815 | 10 | |
| 790 | 13 | |
| 784 | 14 | F784L, |
| 751 | 13 | V751I, V751F, |
| 796 | 9 | |
| 736 | 13 | L736P, |
| 785 | 14 | D785N, |
| 730 | 8 | N730K, |
| 789 | 11 | V789A, V789I |
| 753 | 7 | |
| 1347 | 12 | |
| 729 | 13 | p.L729del, |
| 795 | 6 | |
| 748 | 14 | M748I, |
| 799 | 11 | |
| 787 | 13 | |
| 794 | 11 | |
| 804 | 13 |