SCN5A Variant D1055G

Summary of observed carriers, functional annotations, and structural context for SCN5A D1055G. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

7%

0/11 effective observations

Estimated BrS1 penetrance

51%

5/11 effective observations

Total carriers

1

1 BrS1 · 0 LQT3 · 0 unaffected

D1055G 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 (%)
-4.26 0.219 -2.02 0.94 60 0

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 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)
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 D1055G.
Neighbour residue Distance (Å) Observed variants
1040 15 G1040R, G1040R,
1041 14 D1041G, D1041N,
1042 14
1043 13 E1043K,
1044 13
1045 12 V1045M,
1046 11
1047 11 c.3140_3141dupTG,
1048 10 p.P1048SfsX96, c.3142_3143insTG, P1048S,
1049 9
1050 8 p.A1050CfsX9, A1050T, p.A1050DfsX9,
1051 8 V1051A,
1052 7 A1052D, p.A1052CfsX7
1053 5 E1053K,
1054 4
1055 0 D1055G,
1056 4 T1056A,
1057 5
1058 7 c.3171_3172delTGinsA,
1059 8 Q1059X,
1060 8
1061 9 E1061D, E1061D,
1062 10 D1062H,
1063 11 E1063G,
1064 11 p.E1064del,
1065 12
1066 13 S1066G,
1067 13 L1067R,
1068 14 G1068A, G1068D,
1069 14 T1069M,
1070 15