SCN5A Variant F181L

Summary of observed carriers, functional annotations, and structural context for SCN5A F181L. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

4%

0/10 effective observations

Estimated BrS1 penetrance

38%

3/10 effective observations

Total carriers

0

0 BrS1 · 0 LQT3 · 0 unaffected

F181L has not been reported in gnomAD. This residue resides in a Hotspot region for Brugada syndrome and a Non_Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 3 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 0.974 53 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 12 0 3 – –

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 F181L.
Neighbour residue Distance (Å) Observed variants
175 13 K175N, K175N,
113 6 V113I, V113A,
188 11
178 11 A178G,
179 11 R179X, R179Q,
177 8 L177P,
189 13
121 11 R121W, R121Q,
198 13
124 15 A124D,
118 13
181 0
176 7
172 12
174 13 V174I,
185 7 A185T, A185V,
115 10 S115G,
186 11
182 5 C182R, C182Y,
173 11
112 11 Y112C,
114 6
184 8 H184R,
116 13
187 12 T187S, T187S, T187I
180 5 G180V,
120 15
183 7