SCN5A Variant D356N
Summary of observed carriers, functional annotations, and structural context for SCN5A D356N. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
3%
0/20 effective observations
Estimated BrS1 penetrance
71%
14/20 effective observations
Total carriers
10
9 BrS1 · 0 LQT3 · 1 unaffected
Variant features alone are equivalent to phenotyping 5 individuals for Brugada syndrome and 0 individuals for LQT3.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
|---|---|---|---|---|---|
| -4.91 | 1 | -1.11 | 0.961 | 74 | 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
| Source | Year | Carriers | Unaffected | LQT3 | BrS1 | Other | Other Disease |
|---|---|---|---|---|---|---|---|
| 16325048 | 2005 | 1 | 0 | 1 | 0 | ||
| 22885917 | 2012 | 2 | 0 | 2 | 0 | ||
| 26173111 | 2015 | 1 | 0 | 1 | 0 | ||
| 20129283 | 2010 | 8 | 0 | 8 | 0 | ||
| 29325976 | 2018 | 2 | 0 | 2 | 0 | ||
| 29325976 | 2018 | 2 | 0 | 2 | 0 | ||
| 29574140 | 2018 | 1 | 0 | 1 | 0 | ||
| 30059973 | 2018 | 3 | 3 | 0 | 0 | ||
| Literature, cohort, and gnomAD | – | 10 | 1 | 0 | 9 | – | |
| Variant features alone | – | 15 | 10 | 0 | 5 | – | – |
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) |
|---|---|---|---|---|---|---|
| 16325048 | 2005 | HEK | 0 | |||
| 22885917 | 2012 | |||||
| 26173111 | 2015 | |||||
| 20129285 | 2010 | |||||
| 20188230 | 2010 | |||||
| 20129283 | 2010 | |||||
| 29325976 | 2018 | |||||
| 29325976 | 2018 | |||||
| 29574140 | 2018 | |||||
| 30059973 | 2018 |
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 |
|---|---|---|
| 364 | 11 | |
| 277 | 7 | |
| 271 | 12 | L271V, |
| 266 | 11 | L266H, |
| 276 | 9 | L276Q, L276P, |
| 363 | 12 | |
| 348 | 12 | P348A, |
| 270 | 10 | Q270K, |
| 360 | 7 | |
| 279 | 15 | |
| 1552 | 10 | Q1552L, Q1552R |
| 355 | 7 | F355C, F355I, |
| 1549 | 6 | |
| 278 | 13 | H278D, H278R, |
| 1556 | 15 | |
| 356 | 0 | D356N, |
| 361 | 7 | |
| 904 | 15 | W904X, |
| 343 | 11 | |
| 365 | 13 | |
| 384 | 15 | S384T, |
| 354 | 5 | |
| 1546 | 12 | M1546T, |
| 1545 | 13 | |
| 349 | 15 | D349N, |
| 267 | 13 | |
| 1550 | 6 | |
| 357 | 4 | |
| 272 | 9 | |
| 274 | 7 | G274C, |
| 362 | 12 | |
| 273 | 6 | |
| 1553 | 14 | S1553R, |
| 269 | 7 | |
| 345 | 12 | |
| 275 | 10 | N275K, |
| 912 | 15 | Q912R, |
| 347 | 9 | |
| 1548 | 9 | G1548K, E1548K, |
| 351 | 10 | G351D, G351C, G351S, G351V, |
| 265 | 11 | A265V, |
| 350 | 15 | H350Q, |
| 358 | 9 | |
| 1551 | 9 | D1551Y, D1551N, |
| 346 | 11 | E346D, E346X, E346G, E346K, |
| 359 | 8 | A359T, p.A359PfsX12, |
| 1547 | 11 | V1547L, |
| 344 | 12 | A344S, |
| 381 | 14 | c.1140+1G>A, c.1141-3C>A, |
| 352 | 10 | Y352C, |
| 380 | 15 | |
| 268 | 9 | G268S, |
| 377 | 14 | |
| 353 | 9 | T353I, |
| 1623 | 15 | c.4867delC, R1623Q, R1623L, R1623X, |