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

D785N has not been reported in gnomAD. This residue resides in a Hotspot region for Brugada syndrome and a Non_Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 4 individuals for Brugada syndrome and 0 individuals for LQT3.

In silico predictors

Variant-level computational 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

Observed carriers by publication or cohort.
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.

Published electrophysiology measurements.
PubMed ID Year Cell Type Peak Current (% WT) V1/2 Activation (mV) V1/2 Inactivation (mV) Late/Persistent Current (% WT)
24581105 2014
32533946 2020 HEK 39 11.8 -7.1

Nearby variants

Neighbouring residues within 15 Ångström provide structural context. Variants listed in the right-most column have been observed clinically or in gnomAD.

Previously observed variants near D785N.
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