SCN5A Variant F133L

Summary of observed carriers, functional annotations, and structural context for SCN5A F133L. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

4%

0/10 effective observations

Estimated BrS1 penetrance

33%

3/10 effective observations

Total carriers

0

0 BrS1 · 0 LQT3 · 0 unaffected

F133L 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 0.785 44 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 F133L.
Neighbour residue Distance (Å) Observed variants
231 14 c.692_693delCA,
198 15
124 10 A124D,
131 7
164 14 F164L, F164L, F164L,
130 6
170 8 F170I,
228 13 K228R,
138 9 M138I, M138I, M138I,
171 7
137 6 I137V,
142 14
197 13
129 8
169 13
177 13 L177P,
123 12 A123G, A123V,
127 6
125 10 V125L, V125L,
232 14 V232I, V232F
174 8 V174I,
133 0
132 6 c.393-5C>A,
134 4 N134S,
166 13 A166T,
179 14 R179X, R179Q,
172 11
139 10 p.I137_C139dup,
126 11 K126E,
136 6 L136P,
168 11
175 9 K175N, K175N,
194 15
141 12 I141V, I141N,
135 8 M135V,
167 10
178 12 A178G,
128 6 c.381dupT,
225 13 R225W, R225Q,
176 14
173 12
140 10