SCN5A Variant Y159C

Summary of observed carriers, functional annotations, and structural context for SCN5A Y159C. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

0%

0/16 effective observations

Estimated BrS1 penetrance

15%

2/16 effective observations

Total carriers

6

0 BrS1 · 0 LQT3 · 6 unaffected

Y159C is present in 6 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 (%)
-2.77 1 -1.68 0.886 24 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 – 6 6 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 Y159C.
Neighbour residue Distance (Å) Observed variants
208 13 E208K
154 14 P154L,
156 10 W156R, W156R, W156X,
168 15
158 7 K158T,
163 7 c.486delC,
166 12 A166T,
167 13
161 7 E161K, E161Q,
144 13
151 13
146 15 V146M, V146A,
159 0 Y159C, Y159X,
153 15
155 10
147 10
150 13
164 9 F164L, F164L, F164L,
157 5 T157I,
143 13
148 15
160 4 p.V160fs,
165 11
140 14
162 7 Y162H, Y162C,