SCN5A Variant V125A

Summary of observed carriers, functional annotations, and structural context for SCN5A V125A. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

4%

0/10 effective observations

Estimated BrS1 penetrance

26%

2/10 effective observations

Total carriers

0

0 BrS1 · 0 LQT3 · 0 unaffected

V125A 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 2 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 0.795 34 1

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 13 0 2 – –

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 V125A.
Neighbour residue Distance (Å) Observed variants
126 5 K126E,
175 9 K175N, K175N,
113 14 V113I, V113A,
129 6
188 13
178 5 A178G,
128 6 c.381dupT,
117 13
179 7 R179X, R179Q,
119 10 P119S, P119L,
177 8 L177P,
123 5 A123G, A123V,
121 6 R121W, R121Q,
127 6
124 4 A124D,
118 11
125 0 V125L, V125L,
176 11
172 13
131 13
174 8 V174I,
133 10
115 12 S115G,
173 11
132 14 c.393-5C>A,
112 13 Y112C,
114 11
130 10
184 13 H184R
116 10
180 11 G180V,
134 12 N134S,
170 13 F170I,
120 9
122 7
171 13