SCN5A Variant P234S

Summary of observed carriers, functional annotations, and structural context for SCN5A P234S. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

5%

0/14 effective observations

Estimated BrS1 penetrance

11%

1/14 effective observations

Total carriers

4

0 BrS1 · 0 LQT3 · 4 unaffected

P234S is present in 4 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 1 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 -0.74 None 16 9

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 – 4 4 0 0 –
Variant features alone – 15 14 0 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 P234S.
Neighbour residue Distance (Å) Observed variants
848 14 I848F
937 15
839 11 L839P,
842 11
240 12 V240M,
231 9 c.692_693delCA,
237 10
228 14 K228R,
138 14 M138I, M138I, M138I,
836 10 V836M,
234 0 P234S,
229 12
845 11 c.2533delG,
232 7 V232I, V232F,
833 14 G833R, G833R,
420 15
241 14
235 4 c.703+1G>A, G235R, G235R, c.704-1G>C,
840 8
843 12 T843A,
419 15 Q419X,
423 14
834 14 N834D,
837 7
239 10 I239V, I239V ,
230 10 I230V, I230T, I230M,
841 6 p.N841TfsX2, N841K, N841K,
236 7
238 10
233 5
838 8
135 14 M135V,
844 9 L844RfsX3,
835 12 S835A, S835L,