SCN5A Variant G1040R

Summary of observed carriers, functional annotations, and structural context for SCN5A G1040R. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

5%

0/12 effective observations

Estimated BrS1 penetrance

5%

0/12 effective observations

Total carriers

2

0 BrS1 · 0 LQT3 · 2 unaffected

G1040R is present in 1 alleles in gnomAD. This residue resides in a Non_Hotspot region for Brugada syndrome and a Non_Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 0 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 (%)
-0.4 0.005 -1.15 0.485 2 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
20129283 2010 1 0 0 0
Literature, cohort, and gnomAD – 2 2 0 0 –
Variant features alone – 15 15 0 0 – –

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 G1040R.
Neighbour residue Distance (Å) Observed variants
1025 15 E1025A,
1026 14
1027 14 R1027P, R1027W, R1027Q,
1028 13
1029 13 E1029K,
1030 12
1031 11 p.G1031fsX27,
1032 11 E1032D, E1032D, E1032K,
1033 10 Q1033R,
1034 9 P1034T,
1035 8 G1035V,
1036 8
1037 7
1038 5
1039 4
1040 0 G1040R, G1040R,
1041 4 D1041N, D1041G,
1042 5
1043 7 E1043K,
1044 8
1045 8 V1045M,
1046 9
1047 10 c.3140_3141dupTG,
1048 11 P1048S, c.3142_3143insTG, p.P1048SfsX96,
1049 11
1050 12 A1050T, p.A1050DfsX9, p.A1050CfsX9,
1051 13 V1051A,
1052 13 p.A1052CfsX7, A1052D,
1053 14 E1053K,
1054 14
1055 15 D1055G,