SCN5A Variant D785N
Summary of observed carriers, functional annotations, and structural context for SCN5A D785N. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
2%
0/12 effective observations
Estimated BrS1 penetrance
53%
6/12 effective observations
Total carriers
2
2 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 (%) |
---|---|---|---|---|---|
-4.95 | 0.961 | -2.43 | 0.971 | 65 | 1 |
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 |
---|---|---|---|---|---|---|---|
24581105 | 2014 | 2 | 0 | 2 | 0 | ||
Literature, cohort, and gnomAD | – | 2 | 0 | 0 | 2 | – | |
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 |
---|---|---|
719 | 13 | |
723 | 10 | I723V, |
766 | 13 | |
758 | 13 | G758E, |
811 | 14 | c.2435_2436+3delTGGTAinsCGCCT, R811H, R811G, |
821 | 13 | |
769 | 15 | |
773 | 14 | P773S, |
760 | 8 | p.F760SfsX5, |
776 | 8 | p.Y776del, |
780 | 8 | |
765 | 11 | |
812 | 14 | L812Q, |
759 | 12 | p.I759FfsX6, c.2274delG, I759V, |
792 | 11 | |
764 | 6 | M764R, M764K, |
777 | 10 | F777L, F777L, F777L, |
791 | 11 | L791F, |
819 | 12 | |
726 | 13 | |
818 | 11 | |
781 | 7 | W781X, |
720 | 11 | |
788 | 5 | I788V, |
724 | 12 | T724I, |
782 | 6 | N782T, |
793 | 13 | L793F, |
820 | 10 | |
762 | 11 | |
810 | 13 | |
727 | 11 | |
767 | 9 | |
770 | 15 | |
756 | 14 | |
814 | 9 | R814Q, |
816 | 11 | F816Y, F816L, F816L, F816L, |
722 | 14 | |
813 | 9 | c.2437-5C>A, c.2436+12G>A, |
757 | 12 | |
768 | 10 | |
786 | 5 | |
817 | 6 | K817E, |
761 | 10 | |
779 | 10 | Q779K, Q779X, |
815 | 11 | |
778 | 14 | |
790 | 10 | |
784 | 4 | F784L, F784L, F784L, |
763 | 10 | E763D, E763D, E763K, |
771 | 13 | L771V, |
785 | 0 | D785N, |
783 | 7 | I783T, |
730 | 14 | N730K, N730K, |
789 | 7 | V789A, V789I, |
714 | 13 | V714D, V714A, |
787 | 7 | |
794 | 15 |