SCN5A Variant A185V

Summary of observed carriers, functional annotations, and structural context for SCN5A A185V. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

0%

0/15 effective observations

Estimated BrS1 penetrance

18%

2/15 effective observations

Total carriers

5

1 BrS1 · 0 LQT3 · 4 unaffected

A185V is present in 4 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 (%)
-1.71 0.873 -3.32 0.603 16 2

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
20129283 2010 1 0 1 0
Literature, cohort, and gnomAD – 5 4 0 1 –
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)
20129283 2010

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 A185V.
Neighbour residue Distance (Å) Observed variants
192 13
175 10 K175N,
202 13 I202T,
197 12
113 10 V113I, V113A,
194 10
188 5
178 11 A178G,
196 14
190 9 R190G, R190Q, R190L, R190W,
201 14
179 10 R179Q, R179X,
177 11 L177P,
189 6
121 14 R121W, R121Q,
198 9
181 7
176 7
172 11
174 13 V174I,
185 0 A185V, A185T,
199 12 S199T,
186 5
195 11
182 6 C182Y, C182R,
173 12
112 13 Y112C,
114 11
184 5 H184R,
191 10
187 5 T187S, T187I,
180 6 G180V,
183 6
171 14