SCN5A Variant C1004R

Summary of observed carriers, functional annotations, and structural context for SCN5A C1004R. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

2%

1/81 effective observations

Estimated BrS1 penetrance

2%

1/81 effective observations

Total carriers

71

0 BrS1 · 1 LQT3 · 70 unaffected

C1004R is present in 70 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 (%)
-3.86 0.998 -0.78 0.723 6 2

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
19716085 2009 1 1 0 0
Literature, cohort, and gnomAD – 71 70 1 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)
19716085 2009

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 C1004R.
Neighbour residue Distance (Å) Observed variants
989 15
990 14
991 14 K991E, K991T,
992 13
993 13 A993T, A993S,
994 12 A994V, A994T,
995 11 L995F,
996 11 A996T,
997 10 A997T, A997D, A997S,
998 9
999 8 G999D,
1000 8 Q1000X, p.Gln1000del, Q1000L,
1001 7
1002 5 c.3005-3012delCCAGCTGG, P1002S,
1003 4
1004 0 C1004R,
1005 4 I1005T, I1005V,
1006 5 A1006S,
1007 7 T1007N, T1007I,
1008 8 P1008S,
1009 8
1010 9
1011 10 P1011L, P1011S,
1012 11
1013 11
1014 12 P1014S,
1015 13 p.G1015DfsX14, E1015K,
1016 13 c.3045_3046delGA, T1016M,
1017 14
1018 14 K1018E,
1019 15