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 | R811G, R811H, c.2435_2436+3delTGGTAinsCGCCT, |
808 | 12 | R808P, R808H, R808C, |
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 | M764R, M764K, |
791 | 8 | L791F, |
1344 | 13 | F1344S, F1344L, |
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 | F816L, F816Y, |
813 | 0 | c.2436+12G>A, c.2437-5C>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 | V789A, V789I, |
753 | 14 | |
1347 | 9 | |
795 | 12 | |
829 | 14 | |
787 | 8 | |
794 | 13 |