SCN5A Variant Y774D
Summary of observed carriers, functional annotations, and structural context for SCN5A Y774D. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
21%
1/11 effective observations
Estimated BrS1 penetrance
26%
2/11 effective observations
Total carriers
1
0 BrS1 · 0 LQT3 · 1 unaffected
Variant features alone are equivalent to phenotyping 2 individuals for Brugada syndrome and 1 individuals for LQT3.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
|---|---|---|---|---|---|
| -9.73 | 0.979 | -2.71 | 0.919 | 32 | 23 |
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 |
|---|---|---|---|---|---|---|---|
| Literature, cohort, and gnomAD | – | 1 | 1 | 0 | 0 | – | |
| Variant features alone | – | 15 | 12 | 1 | 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.
| Neighbour residue | Distance (Å) | Observed variants |
|---|---|---|
| 774 | 0 | Y774D, Y774C, c.2320delT, p.Y774TfsX28, |
| 772 | 5 | D772N, |
| 767 | 14 | |
| 770 | 12 | |
| 775 | 6 | |
| 771 | 10 | L771V, |
| 783 | 13 | I783T, |
| 769 | 12 | |
| 773 | 4 | P773S, |
| 776 | 9 | p.Y776del, |
| 768 | 10 | |
| 786 | 15 | |
| 779 | 13 | Q779K, Q779X, |
| 777 | 8 | F777L, |
| 782 | 13 | N782T, |
| 778 | 9 |