SCN5A Variant C139S

Summary of observed carriers, functional annotations, and structural context for SCN5A C139S. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

3%

0/10 effective observations

Estimated BrS1 penetrance

41%

4/10 effective observations

Total carriers

0

0 BrS1 · 0 LQT3 · 0 unaffected

C139S has not been reported in gnomAD. This residue resides in a Hotspot region for Brugada syndrome and a Non_Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 4 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 (%)
NA NA NA 0.735 59 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 – 0 0 0 0 –
Variant features alone – 15 11 0 4 – –

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 C139S.
Neighbour residue Distance (Å) Observed variants
231 12 c.692_693delCA,
147 13
131 12
164 10 F164L, F164L, F164L,
130 14
170 15 F170I,
228 12 K228R,
138 5 M138I, M138I, M138I,
227 15 L227P,
171 13
143 6
137 6 I137V,
142 5
229 10
163 13 c.486delC,
232 10 V232I, V232F
133 10
132 10 c.393-5C>A,
160 14 p.V160fs,
134 9 N134S,
226 12 A226G, A226V,
166 15 A166T,
144 10
230 14 I230V, I230T, I230M,
139 0 p.I137_C139dup,
148 14
165 15
146 11 V146M, V146A,
136 5 L136P,
168 11
233 14
141 6 I141V, I141N,
135 7 M135V,
167 11
225 11 R225W, R225Q,
145 10
140 5