SCN5A Variant R1023C

Summary of observed carriers, functional annotations, and structural context for SCN5A R1023C. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

2%

0/15 effective observations

Estimated BrS1 penetrance

8%

1/15 effective observations

Total carriers

5

0 BrS1 · 0 LQT3 · 5 unaffected

R1023C is present in 5 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 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 (%)
-0.31 0.996 -1.65 0.813 2 3

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
23168001 2013 1 0 0 1 IVF
30059973 2018 2 2 0 0
Literature, cohort, and gnomAD – 5 5 0 0 –
Variant features alone – 15 14 0 1 – –

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)
23168001 2013
30059973 2018

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 R1023C.
Neighbour residue Distance (Å) Observed variants
1008 15 P1008S,
1009 14
1010 14
1011 13 P1011L, P1011S,
1012 13
1013 12
1014 11 P1014S,
1015 11 p.G1015DfsX14, E1015K,
1016 10 c.3045_3046delGA, T1016M,
1017 9
1018 8 K1018E,
1019 8
1020 7
1021 5 P1021S,
1022 4
1023 0 R1023H, R1023P, R1023C,
1024 4 K1024R,
1025 5 E1025A,
1026 7
1027 8 R1027P, R1027Q, R1027W,
1028 8
1029 9 E1029K,
1030 10
1031 11 p.G1031fsX27,
1032 11 E1032D, E1032D, E1032K,
1033 12 Q1033R,
1034 13 P1034T,
1035 13 G1035V,
1036 14
1037 14
1038 15