SCN5A Variant G857D

Summary of observed carriers, functional annotations, and structural context for SCN5A G857D. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

4%

0/13 effective observations

Estimated BrS1 penetrance

13%

1/13 effective observations

Total carriers

3

0 BrS1 · 0 LQT3 · 3 unaffected

G857D is present in 3 alleles in gnomAD. This residue resides in a Mild_Hotspot region for Brugada syndrome and a Non_Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 1 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 (%)
-6.93 1 -4.19 0.982 13 5

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
Literature, cohort, and gnomAD – 3 3 0 0 –
Variant features alone – 15 14 0 1 – –

Totals may differ from individual publications due to duplicate patients removed during curation.

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 G857D.
Neighbour residue Distance (Å) Observed variants
891 9 I891N, I891T,
880 11
888 11
848 15 I848F,
223 10 V223L,
856 4 V856L, V856L,
890 9 I890T,
919 9
862 7
867 15 E867Q, E867X, E867K,
859 6
894 12 I894M,
149 13
863 11
887 7
864 10
886 11 H886Q, H886Q, H886P,
216 11 S216X, S216L,
851 10 p.F851CfsX19, F851L, F851L, c.2550_2551dupGT, F851L, c.2552_2553dupGT,
221 10
909 13
852 9
854 5 c.2559delT,
222 13 R222L, R222X, R222Q,
224 12 L224F,
857 0 G857D,
902 12
882 10
892 14 F892I,
881 5
849 13
226 15 A226V, A226G,
893 15 R893C, R893H,
921 12
922 11 V922I,
860 5 p.L860fsx89,
911 14 G911E,
920 14
889 12
858 5 M858L, M858L,
217 11
918 8
855 6
917 13 L917V, L917R,
865 10
913 13
916 14
148 12
884 10
906 10
866 14 S866P, S866L,
910 11 S910L,
885 13
903 13 p.M903CfsX29,
152 13 D152N,
853 8
219 11 R219H, c.656_657insATTCA, R219C, p.R219HfsX11,
877 15
151 13
879 14 W879R, W879R,
218 14
883 10
905 14
915 9 C915R,
215 14 p.L215CfsX10,
850 11 V850M, c.2549_2550insTG,
914 9
145 15
861 5 c.2582_2583delTT, p.F861WfsX90,
220 8 T220I,
907 14