SCN5A Variant Y112C

Summary of observed carriers, functional annotations, and structural context for SCN5A Y112C. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

20%

1/11 effective observations

Estimated BrS1 penetrance

10%

1/11 effective observations

Total carriers

1

0 BrS1 · 0 LQT3 · 1 unaffected

Y112C is present in 1 alleles 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 1 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 (%)
-7.36 0.95 2.22 0.925 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 – 1 1 0 0 –
Variant features alone – 15 13 1 1 – –

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