SCN5A Variant N134S

Summary of observed carriers, functional annotations, and structural context for SCN5A N134S. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

0%

0/11 effective observations

Estimated BrS1 penetrance

9%

1/11 effective observations

Total carriers

1

0 BrS1 · 0 LQT3 · 1 unaffected

N134S is present in 1 alleles in gnomAD. This residue resides in a Mild_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 (%)
1.77 0 1.07 0.233 18 0

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
Literature, cohort, and gnomAD – 1 1 0 0 –
Variant features alone – 15 14 0 1 – –

Totals may differ from individual publications due to duplicate patients removed during curation.

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 N134S.
Neighbour residue Distance (Å) Observed variants
231 10 c.692_693delCA,
198 15
124 12 A124D,
131 5
193 15 W193R, W193R, W193X,
130 7
170 12 F170I,
228 10 K228R,
138 7 M138I, M138I, M138I,
171 9
143 15
137 6 I137V,
142 13
197 12
229 12
129 7
123 15 A123G, A123V,
127 9
125 12 V125L, V125L,
232 10 V232I, V232F
174 11 V174I,
133 4
132 7 c.393-5C>A,
134 0 N134S,
226 15 A226G, A226V,
179 14 R179X, R179Q,
172 13
230 14 I230V, I230T, I230M,
139 9 p.I137_C139dup,
126 13 K126E,
136 7 L136P,
168 12
175 10 K175N, K175N,
233 15
194 13
141 11 I141V, I141N,
135 5 M135V,
167 12
178 13 A178G,
128 7 c.381dupT,
225 12 R225W, R225Q,
173 15
140 11