SCN5A Variant C145S

Summary of observed carriers, functional annotations, and structural context for SCN5A C145S. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

4%

0/10 effective observations

Estimated BrS1 penetrance

12%

1/10 effective observations

Total carriers

0

0 BrS1 · 0 LQT3 · 0 unaffected

C145S has not been reported 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 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 (%)
NA NA NA 0.949 6 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 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 C145S.
Neighbour residue Distance (Å) Observed variants
888 14
848 10 I848F,
223 8 V223L,
856 13 V856L, V856L,
859 14
231 14 c.692_693delCA,
153 15
149 7
147 7
164 10 F164L, F164L, F164L,
228 12 K228R,
138 10 M138I, M138I, M138I,
227 11 L227P,
143 6
887 14
137 13 I137V,
142 5
229 9
163 15 c.486delC,
851 7 c.2550_2551dupGT, F851L, p.F851CfsX19, c.2552_2553dupGT, F851L, F851L,
221 15
852 9
854 11 c.2559delT,
222 10 R222X, R222Q, R222L,
224 11 L224F,
845 14 c.2533delG,
857 15 G857D,
150 10
232 14 V232I, V232F,
157 14 T157I,
160 13 p.V160fs,
849 13
226 7 A226G, A226V,
858 12 M858L, M858L
144 4
855 9
230 13 I230V, I230T, I230M,
139 10 p.I137_C139dup,
148 5
165 15
884 10
885 14
146 5 V146M, V146A,
847 11
136 15 L136P,
168 13
152 13 D152N,
141 6 I141V, I141N,
167 15
853 14
161 12 E161K, E161Q,
219 14 p.R219HfsX11, R219C, c.656_657insATTCA, R219H,
225 10 R225W, R225Q,
151 10
844 13 L844RfsX3,
850 12 V850M, c.2549_2550insTG,
200 14
145 0
140 9
220 14 T220I,