SCN5A Variant Y112F

Summary of observed carriers, functional annotations, and structural context for SCN5A Y112F. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

21%

1/10 effective observations

Estimated BrS1 penetrance

7%

0/10 effective observations

Total carriers

0

0 BrS1 · 0 LQT3 · 0 unaffected

Y112F has not been reported in gnomAD. This residue resides in a Non_Hotspot region for Brugada syndrome and a Mild_Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 0 individuals for Brugada syndrome and 1 individuals for LQT3.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density BrS (%) Penetrance Density LQT3 (%)
-3.15 0.189 6.48 0.784 5 19

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 14 1 0 – –

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)
29734505 2018 HEK 1.7 4

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 Y112F.
Neighbour residue Distance (Å) Observed variants
113 5 V113I, V113A,
188 14
178 11 A178G,
117 9
119 15 P119S, P119L,
179 9 R179X, R179Q,
177 12 L177P,
121 10 R121W, R121Q,
118 11
125 13 V125L, V125L,
181 11
176 13
185 13 A185T, A185V,
115 7 S115G,
186 14
182 10 C182R, C182Y,
112 0 Y112C,
114 7
184 7 H184R,
116 6
187 12 T187S, T187S, T187I
180 8 G180V,
183 8
122 12