SCN5A Variant Y416S

Summary of observed carriers, functional annotations, and structural context for SCN5A Y416S. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

10%

0/10 effective observations

Estimated BrS1 penetrance

25%

2/10 effective observations

Total carriers

0

0 BrS1 · 0 LQT3 · 0 unaffected

Y416S has not been reported 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 (%)
NA NA NA 0.969 30 10

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 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 Y416S.
Neighbour residue Distance (Å) Observed variants
414 9 M414V,
939 9 L939F,
937 7
839 12 L839P,
842 10
249 12 K249X,
943 13 S943N,
247 13 V247L, V247L,
240 11 V240M,
418 8 E418K,
250 15
409 11 L409V, L409P,
237 12
928 15 L928P,
417 5
934 10
933 6
246 9
935 10 L935P,
1779 15 T1779M
412 7 V412D,
1470 14
245 10 Q245K,
1776 14
845 13 c.2533delG,
244 12
415 6 A415T,
940 7 S940N,
420 5
938 10
241 9
235 12 c.703+1G>A, G235R, G235R, c.704-1G>C,
840 13
942 13
843 14 T843A,
419 6 Q419X,
930 11 c.2787+17_2787+18insACACACACACACACACACACACA, c.2788-6C>T,
423 10
1772 14 L1772V,
837 13
239 7 I239V, I239V ,
410 11 A410V,
242 6 A242D,
929 11
416 0 Y416C,
413 6 A413T, A413E,
841 12 p.N841TfsX2, N841K, N841K,
236 13
408 14
941 10 S941N, S941F,
846 15 L846R,
936 5
238 7
838 10
422 10
1467 14
1775 15 F1775V, p.F1775LfsX15,
421 9
411 11 V411M,
243 9
932 11
835 13 S835A, S835L,
931 13
1463 15 N1463Y,