SCN5A Variant A149V

Summary of observed carriers, functional annotations, and structural context for SCN5A A149V. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

12%

0/10 effective observations

Estimated BrS1 penetrance

12%

1/10 effective observations

Total carriers

0

0 BrS1 · 0 LQT3 · 0 unaffected

A149V 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 (%)
-1.04 0.993 -1.75 0.912 7 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
24631775 2014 1 0 0 1 SIDS
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.

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)
24631775 2014

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 A149V.
Neighbour residue Distance (Å) Observed variants
888 12
154 10 P154L,
848 14 I848F,
223 12 V223L,
856 13 V856L, V856L,
862 15
859 12
1447 14
1444 14 L1444I
153 8
149 0
147 7
164 14 F164L, F164L, F164L,
887 11
143 10
142 12
156 11 W156R, W156R, W156X,
886 13 H886P, H886Q, H886Q,
851 9 c.2550_2551dupGT, F851L, p.F851CfsX19, c.2552_2553dupGT, F851L, F851L,
222 13 R222X, R222Q, R222L,
852 13
854 10 c.2559delT,
155 11
857 13 G857D,
150 4
157 12 T157I,
882 12
160 13 p.V160fs,
881 14
226 13 A226G, A226V,
889 15
858 9 M858L, M858L,
144 9
855 9
148 5
884 6
885 9
146 5 V146M, V146A,
847 15
152 6 D152N,
141 13 I141V, I141N,
161 13 E161K, E161Q,
219 13 p.R219HfsX11, R219C, c.656_657insATTCA, R219H,
151 5
883 9
850 14 V850M, c.2549_2550insTG,
145 7
140 15
220 15 T220I,