SCN5A Variant c.2550_2551dupGT

Summary of observed carriers, functional annotations, and structural context for SCN5A c.2550_2551dupGT. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

27%

1/11 effective observations

Estimated BrS1 penetrance

36%

3/11 effective observations

Total carriers

1

1 BrS1 · 0 LQT3 · 0 unaffected

c.2550_2551dupGT has not been reported in gnomAD. This residue resides in a Mild_Hotspot region for Brugada syndrome and a Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 2 individuals for Brugada syndrome and 1 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 39 43

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
20129283 2010 1 0 1 0
Literature, cohort, and gnomAD – 1 0 0 1 –
Variant features alone – 15 12 1 2 – –

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)
20129283 2010

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.2550_2551dupGT.
Neighbour residue Distance (Å) Observed variants
891 10 I891N, I891T,
888 8
848 6 I848F,
223 7 V223L,
856 9 V856L, V856L,
890 13 I890T,
859 13
895 13 L895F,
894 14 I894M,
1447 14
149 9
147 12
926 14
228 13 K228R,
138 15 M138I, M138I, M138I,
925 14 I925F,
227 10 L227P,
143 13
887 9
1451 14 V1451L, V1451D
142 11
886 14 H886P, H886Q, H886Q,
229 10
851 0 c.2550_2551dupGT, F851L, p.F851CfsX19, c.2552_2553dupGT, F851L, F851L,
221 13
852 5
854 6 c.2559delT,
222 12 R222X, R222Q, R222L,
224 10 L224F,
845 11 c.2533delG,
857 10 G857D,
150 13
892 12 F892I,
881 13
849 8
226 7 A226G, A226V,
922 13 V922I,
860 14 p.L860fsx89,
889 12
843 13 T843A,
858 10 M858L, M858L,
144 10
918 15
855 6
230 12 I230V, I230T, I230M,
148 8
1448 15 I1448L, I1448T,
884 7
885 11
146 10 V146M, V146A,
847 7
846 10 L846R,
233 15
152 13 D152N,
141 11 I141V, I141N,
853 8
219 15 p.R219HfsX11, R219C, c.656_657insATTCA, R219H,
225 12 R225W, R225Q,
151 12
883 13
844 11 L844RfsX3,
850 6 V850M, c.2549_2550insTG,
145 7
220 13 T220I,