SCN5A Variant Y416C
Summary of observed carriers, functional annotations, and structural context for SCN5A Y416C. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
8%
0/12 effective observations
Estimated BrS1 penetrance
31%
3/12 effective observations
Total carriers
2
1 BrS1 · 0 LQT3 · 1 unaffected
Variant features alone are equivalent to phenotyping 2 individuals for Brugada syndrome and 0 individuals for LQT3.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
|---|---|---|---|---|---|
| -8.83 | 1 | -6.68 | 0.925 | 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
| Source | Year | Carriers | Unaffected | LQT3 | BrS1 | Other | Other Disease |
|---|---|---|---|---|---|---|---|
| 28341781 | 2017 | 1 | 0 | 1 | 0 | ||
| 28069705 | 2017 | 1 | 0 | 0 | 1 | ARVD | |
| Literature, cohort, and gnomAD | – | 2 | 1 | 0 | 1 | – | |
| Variant features alone | – | 15 | 13 | 0 | 2 | – | – |
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.
Nearby variants
Neighbouring residues within 15 Ångström provide structural context. Variants listed in the right-most column have been observed clinically or in gnomAD.
| 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, |