SCN5A Variant A166S

Summary of observed carriers, functional annotations, and structural context for SCN5A A166S. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

3%

0/10 effective observations

Estimated BrS1 penetrance

13%

1/10 effective observations

Total carriers

0

0 BrS1 · 0 LQT3 · 0 unaffected

A166S has not been reported 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 (%)
NA NA NA 0.696 11 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 A166S.
Neighbour residue Distance (Å) Observed variants
198 14
147 15
164 7 F164L, F164L, F164L,
209 15 N209S, N209T,
170 7 F170I,
171 9
143 14
137 11 I137V,
158 14 K158T,
197 14
163 5 c.486delC,
169 5
222 13 R222X, R222Q, R222L,
174 12 V174I,
133 13
157 15 T157I,
160 10 p.V160fs,
205 10 c.612-2A>G, Y205X,
206 14
166 0 A166T,
144 13
172 10
139 15 p.I137_C139dup,
165 4
204 10 A204T, c.611+1G>A, c.611+3_611+4dupAA, A204V,
162 8 Y162H, Y162C,
208 10 E208K,
136 13 L136P,
168 6
202 13 I202T,
175 14 K175N, K175N,
141 13 I141V, I141N,
167 4
161 10 E161K, E161Q,
201 10
225 13 R225W, R225Q
159 12 Y159C, Y159X,
207 14
173 11
200 14
140 10