SCN5A Variant F164L

Summary of observed carriers, functional annotations, and structural context for SCN5A F164L. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

3%

0/11 effective observations

Estimated BrS1 penetrance

19%

2/11 effective observations

Total carriers

1

0 BrS1 · 0 LQT3 · 1 unaffected

F164L is present in 1 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 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 (%)
-5.78 0.951 -1.61 0.986 23 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 – 1 1 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 F164L.
Neighbour residue Distance (Å) Observed variants
223 13 V223L,
149 14
147 8
164 0 F164L, F164L, F164L,
170 12 F170I,
228 15 K228R,
138 12 M138I, M138I, M138I,
171 11
143 7
137 10 I137V,
142 11
156 14 W156X, W156R, W156R,
158 11 K158T,
197 14
163 5 c.486delC,
169 10
222 9 R222L, R222X, R222Q,
224 15 L224F,
150 13
133 14
157 10 T157I,
160 5 p.V160fs,
226 13 A226V, A226G,
205 14 c.612-2A>G, Y205X,
166 7 A166T,
144 6
172 14
139 10 p.I137_C139dup,
148 10
165 6
204 10 A204T, c.611+1G>A, c.611+3_611+4dupAA, A204V,
162 8 Y162C, Y162H,
146 11 V146A, V146M,
203 15
208 11 E208K,
136 12 L136P,
168 6
202 15 I202T,
141 8 I141N, I141V,
167 6
161 6 E161Q, E161K,
201 11
219 13 p.R219HfsX11, c.656_657insATTCA, R219H, R219C
225 10 R225Q, R225W,
151 12
159 9 Y159X, Y159C,
207 13
200 12
145 10
140 6