SCN5A Variant S1074R

Summary of observed carriers, functional annotations, and structural context for SCN5A S1074R. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

68%

4/11 effective observations

Estimated BrS1 penetrance

7%

0/11 effective observations

Total carriers

1

0 BrS1 · 1 LQT3 · 0 unaffected

S1074R has not been reported in gnomAD. This residue resides in a Non_Hotspot region for Brugada syndrome and a Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 0 individuals for Brugada syndrome and 3 individuals for LQT3.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density BrS (%) Penetrance Density LQT3 (%)
-1.77 0.998 0.35 0.588 4 81

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
26401487 2015 1 1 0 0
Literature, cohort, and gnomAD – 1 0 1 0 –
Variant features alone – 15 12 3 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)
26401487 2015

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 S1074R.
Neighbour residue Distance (Å) Observed variants
1059 15 Q1059X,
1060 14
1061 14 E1061D, E1061D,
1062 13 D1062H,
1063 13 E1063G,
1064 12 p.E1064del,
1065 11
1066 11 S1066G,
1067 10 L1067R,
1068 9 G1068A, G1068D,
1069 8 T1069M,
1070 8
1071 7 E1071K, p.E1071GfsX76,
1072 5 p.E1072del,
1073 4
1074 0 S1074R, S1074R, S1074R, S1074G,
1075 4
1076 5
1077 7 c.3228+2delT,
1078 8
1079 8 S1079F, S1079T, S1079Y,
1080 9
1081 10
1082 11 V1082A,
1083 11 S1083C,
1084 12 G1084S, G1084R, G1084D,
1085 13
1086 13
1087 14
1088 14 A1088T, A1088V,
1089 15