SCN5A Variant c.2559delT

Summary of observed carriers, functional annotations, and structural context for SCN5A c.2559delT. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

8%

0/11 effective observations

Estimated BrS1 penetrance

52%

5/11 effective observations

Total carriers

1

1 BrS1 · 0 LQT3 · 0 unaffected

c.2559delT 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 (%)
NA NA NA None 70 10

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
26921764 2016 1 0 1 0
Literature, cohort, and gnomAD – 1 0 0 1 –
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)
26921764 2016

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 c.2559delT.
Neighbour residue Distance (Å) Observed variants
891 6 I891N, I891T,
880 12
888 7
848 10 I848F,
223 9 V223L,
856 6 V856L, V856L,
890 8 I890T,
919 11
862 11
896 15 C896S, C896S,
859 10
895 12 L895F,
894 11 I894M,
1447 13
149 10
147 15
926 13
925 13 I925F,
227 13 L227P,
887 5
1451 15 V1451L, V1451D
886 10 H886P, H886Q, H886Q,
851 6 c.2550_2551dupGT, F851L, p.F851CfsX19, c.2552_2553dupGT, F851L, F851L,
221 12
852 6
854 0 c.2559delT,
222 13 R222X, R222Q, R222L,
224 12 L224F,
845 14 c.2533delG,
857 5 G857D,
150 14
902 13
882 12
892 11 F892I,
881 8
849 9
226 12 A226G, A226V,
893 13 R893C, R893H,
921 13
922 10 V922I,
860 10 p.L860fsx89,
889 9
858 6 M858L, M858L,
144 14
217 15
918 10
855 4
865 13
148 10
884 6
906 13
885 10
146 14 V146M, V146A,
847 10
846 12 L846R,
152 12 D152N,
853 6
219 13 p.R219HfsX11, R219C, c.656_657insATTCA, R219H,
151 12
879 14 W879R, W879R,
923 14
883 10
915 13 C915R,
850 6 V850M, c.2549_2550insTG,
914 14
145 11
861 10 p.F861WfsX90, c.2582_2583delTT,
220 11 T220I,