SCN5A Variant K317N
Summary of observed carriers, functional annotations, and structural context for SCN5A K317N. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
2%
0/11 effective observations
Estimated BrS1 penetrance
34%
3/11 effective observations
Total carriers
1
1 BrS1 · 0 LQT3 · 0 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 (%) |
|---|---|---|---|---|---|
| -2.38 | 0.002 | -0.89 | 0.518 | 34 | 0 |
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 |
|---|---|---|---|---|---|---|---|
| 14625171 | 2003 | 1 | 0 | 1 | 0 | ||
| Literature, cohort, and gnomAD | – | 1 | 0 | 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.
| PubMed ID | Year | Cell Type | Peak Current (% WT) | V1/2 Activation (mV) | V1/2 Inactivation (mV) | Late/Persistent Current (% WT) |
|---|---|---|---|---|---|---|
| 14625171 | 2003 |
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 |
|---|---|---|
| 343 | 12 | |
| 277 | 13 | |
| 342 | 11 | |
| 346 | 11 | E346K, E346G, E346X, E346D, E346D |
| 319 | 7 | G319S, G319R, G319C, |
| 317 | 0 | K317E, K317M, K317N, K317N, |
| 282 | 14 | R282C, R282H, |
| 279 | 12 | |
| 321 | 10 | S321Y, |
| 344 | 8 | A344S, |
| 340 | 14 | R340W, R340Q, |
| 345 | 8 | |
| 322 | 14 | |
| 280 | 15 | C280Y, |
| 318 | 6 | |
| 281 | 11 | V281M, |
| 323 | 14 | |
| 347 | 15 | |
| 283 | 13 | |
| 320 | 6 | T320N, |