SCN5A Variant R1116Q

Summary of observed carriers, functional annotations, and structural context for SCN5A R1116Q. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

5%

1/31 effective observations

Estimated BrS1 penetrance

0%

0/31 effective observations

Total carriers

21

0 BrS1 · 1 LQT3 · 20 unaffected

R1116Q is present in 20 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 (%)
-0.15 0 2.24 0.351 1 6

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
23631430 2013 1 1 0 0
23571586 2013 1 0 0 1 stillbirth, SUDS
Literature, cohort, and gnomAD – 21 20 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)
23631430 2013
23571586 2013

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 R1116Q.
Neighbour residue Distance (Å) Observed variants
1101 15
1102 14 A1102T,
1103 14 S1103F, S1103Y,
1104 13
1105 13 E1105V, E1105X,
1106 12 A1106T,
1107 11 E1107X, E1107K, p.E1107RfsX24,
1108 11
1109 10 S1109G,
1110 9
1111 8
1112 8 Q1112X,
1113 7 A1113V, A1113T,
1114 5 D1114E, D1114E, D1114N,
1115 4 W1115R, W1115R, W1115X,
1116 0 R1116Q, R1116W,
1117 4
1118 5 Q1118X,
1119 7
1120 8
1121 8 A1121V,
1122 9
1123 10
1124 11
1125 11 A1125T, A1125G, A1125V,
1126 12
1127 13
1128 13 C1128X,
1129 14 G1129S,
1130 14 E1130K,
1131 15 c.3390-1G>A, T1131I, c.3391-1G>A, T1131S, T1131S,