SCN5A Variant c.2437-5C>A
Summary of observed carriers, functional annotations, and structural context for SCN5A c.2437-5C>A. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
43%
3/14 effective observations
Estimated BrS1 penetrance
13%
1/14 effective observations
Total carriers
4
0 BrS1 · 2 LQT3 · 2 unaffected
Variant features alone are equivalent to phenotyping 1 individuals for Brugada syndrome and 1 individuals for LQT3.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
|---|---|---|---|---|---|
| NA | NA | NA | None | 18 | 48 |
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 |
|---|---|---|---|---|---|---|---|
| 28725320 | 2017 | 4 | 2 | 0 | 0 | ||
| 29672598 | 2018 | 1 | 0 | 0 | 1 | SUDS | |
| Literature, cohort, and gnomAD | – | 4 | 2 | 2 | 0 | – | |
| Variant features alone | – | 15 | 13 | 1 | 1 | – | – |
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 |
|---|---|---|
| 811 | 8 | R811H, c.2435_2436+3delTGGTAinsCGCCT, R811G, |
| 808 | 12 | R808H, R808C, R808P, |
| 821 | 15 | |
| 1351 | 11 | M1351V, M1351R, |
| 760 | 12 | p.F760SfsX5, |
| 780 | 13 | |
| 1452 | 15 | |
| 812 | 5 | L812Q, |
| 1350 | 12 | I1350T, I1350L |
| 792 | 10 | |
| 764 | 14 | M764K, M764R, |
| 791 | 8 | L791F, |
| 1344 | 13 | F1344L, F1344S, |
| 731 | 12 | T731I, |
| 806 | 12 | V806M, |
| 819 | 12 | |
| 818 | 11 | |
| 825 | 14 | |
| 781 | 11 | W781X, |
| 1348 | 12 | F1348L, |
| 1349 | 14 | |
| 788 | 6 | I788V, |
| 1346 | 13 | L1346I, L1346P, |
| 805 | 15 | S805L, |
| 782 | 14 | N782T, |
| 793 | 14 | L793F, |
| 728 | 15 | V728I, |
| 820 | 14 | |
| 810 | 6 | |
| 727 | 11 | |
| 1456 | 15 | |
| 734 | 11 | c.2201dupT, M734V, |
| 756 | 15 | |
| 814 | 6 | R814Q, |
| 807 | 10 | |
| 816 | 6 | F816Y, F816L, |
| 813 | 0 | c.2437-5C>A, c.2436+12G>A, |
| 757 | 13 | |
| 786 | 11 | |
| 1354 | 14 | |
| 817 | 9 | K817E, |
| 809 | 7 | |
| 815 | 7 | |
| 790 | 11 | |
| 1343 | 13 | |
| 784 | 7 | F784L, |
| 796 | 15 | |
| 785 | 9 | D785N, |
| 783 | 12 | I783T, |
| 730 | 12 | N730K, |
| 789 | 10 | V789I, V789A, |
| 753 | 14 | |
| 1347 | 9 | |
| 795 | 12 | |
| 829 | 14 | |
| 787 | 8 | |
| 794 | 13 |