SCN5A Variant Q1033R

Summary of observed carriers, functional annotations, and structural context for SCN5A Q1033R. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

24%

1/13 effective observations

Estimated BrS1 penetrance

4%

0/13 effective observations

Total carriers

3

0 BrS1 · 1 LQT3 · 2 unaffected

Q1033R is present in 1 alleles in gnomAD. This residue resides in a Non_Hotspot region for Brugada syndrome and a Mild_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 (%)
-0.34 0 1.66 0.245 0 22

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
26412604 2016 1 0 0 1 syncope
26669661 2016 2 1 0 0
Literature, cohort, and gnomAD – 3 2 1 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)
26412604 2016
26669661 2016

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 Q1033R.
Neighbour residue Distance (Å) Observed variants
1018 15 K1018E,
1019 14
1020 14
1021 13 P1021S,
1022 13
1023 12 R1023P, R1023H, R1023C,
1024 11 K1024R,
1025 11 E1025A,
1026 10
1027 9 R1027P, R1027W, R1027Q,
1028 8
1029 8 E1029K,
1030 7
1031 5 p.G1031fsX27,
1032 4 E1032D, E1032D, E1032K,
1033 0 Q1033R,
1034 4 P1034T,
1035 5 G1035V,
1036 7
1037 8
1038 8
1039 9
1040 10 G1040R, G1040R,
1041 11 D1041N, D1041G,
1042 11
1043 12 E1043K,
1044 13
1045 13 V1045M,
1046 14
1047 14 c.3140_3141dupTG,
1048 15 P1048S, c.3142_3143insTG, p.P1048SfsX96,