SCN5A Variant W1095C

Summary of observed carriers, functional annotations, and structural context for SCN5A W1095C. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

17%

1/14 effective observations

Estimated BrS1 penetrance

8%

1/14 effective observations

Total carriers

4

0 BrS1 · 1 LQT3 · 3 unaffected

W1095C is present in 2 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 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 (%)
-0.88 0.651 0.83 0.606 6 12

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
26669661 2016 2 1 0 0
29574140 2018 1 0 1 0
Literature, cohort, and gnomAD – 4 3 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)
26669661 2016
29574140 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 W1095C.
Neighbour residue Distance (Å) Observed variants
1080 15
1081 14
1082 14 V1082A,
1083 13 S1083C,
1084 13 G1084S, G1084R, G1084D,
1085 12
1086 11
1087 11
1088 10 A1088T, A1088V,
1089 9
1090 8 P1090Q, P1090L,
1091 8 D1091A, D1091Y,
1092 7
1093 5
1094 4
1095 0 W1095X, W1095C, W1095C,
1096 4 S1096C, S1096G,
1097 5 Q1097H, c.3288+2delT, Q1097H,
1098 7 V1098L, V1098L, V1098M,
1099 8
1100 8 A1100T, A1100V,
1101 9
1102 10 A1102T,
1103 11 S1103F, S1103Y,
1104 11
1105 12 E1105V, E1105X,
1106 13 A1106T,
1107 13 p.E1107RfsX24, E1107X, E1107K,
1108 14
1109 14 S1109G,
1110 15