SCN5A Variant S354R
Summary of observed carriers, functional annotations, and structural context for SCN5A S354R. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
12%
0/10 effective observations
Estimated BrS1 penetrance
49%
4/10 effective observations
Total carriers
0
0 BrS1 · 0 LQT3 · 0 unaffected
Variant features alone are equivalent to phenotyping 4 individuals for Brugada syndrome and 0 individuals for LQT3.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
|---|---|---|---|---|---|
| NA | NA | NA | 0.926 | 72 | 12 |
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 | – | 0 | 0 | 0 | 0 | – | |
| Variant features alone | – | 15 | 11 | 0 | 4 | – | – |
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 |
|---|---|---|
| 364 | 8 | |
| 277 | 7 | |
| 271 | 12 | L271V, |
| 266 | 13 | L266H, |
| 276 | 6 | L276Q, L276P, |
| 363 | 9 | |
| 348 | 7 | P348A, |
| 270 | 12 | Q270K, |
| 360 | 7 | |
| 279 | 13 | |
| 385 | 13 | A385T, |
| 355 | 5 | F355I, F355C, |
| 1549 | 11 | |
| 278 | 11 | H278D, H278R, |
| 356 | 5 | D356N, |
| 361 | 7 | |
| 904 | 11 | W904X, |
| 366 | 14 | |
| 343 | 12 | |
| 365 | 11 | |
| 376 | 12 | R376H, R376C, |
| 384 | 12 | S384T, |
| 354 | 0 | |
| 1546 | 15 | M1546T, |
| 378 | 15 | |
| 349 | 10 | D349N, |
| 373 | 15 | |
| 267 | 13 | |
| 379 | 15 | |
| 1550 | 10 | |
| 357 | 7 | |
| 272 | 8 | |
| 274 | 7 | G274C, |
| 362 | 12 | |
| 273 | 9 | |
| 325 | 12 | L325R, |
| 900 | 13 | |
| 392 | 13 | |
| 269 | 9 | |
| 389 | 15 | Y389H, Y389X, |
| 345 | 11 | |
| 393 | 14 | |
| 275 | 9 | N275K, N275K, |
| 264 | 15 | |
| 912 | 14 | Q912R, |
| 323 | 14 | |
| 347 | 6 | |
| 382 | 14 | |
| 1548 | 14 | G1548K, E1548K, |
| 351 | 7 | G351C, G351D, G351V, G351S, |
| 265 | 11 | A265V, |
| 350 | 11 | H350Q, H350Q, |
| 358 | 11 | |
| 903 | 14 | p.M903CfsX29, |
| 367 | 11 | R367C, R367L, R367H, |
| 1551 | 14 | D1551Y, D1551N, |
| 346 | 10 | E346X, E346D, E346D, E346G, E346K, |
| 359 | 9 | A359T, p.A359PfsX12, |
| 344 | 12 | A344S, |
| 381 | 10 | c.1141-3C>A, c.1140+1G>A, |
| 322 | 15 | |
| 352 | 8 | Y352C, |
| 368 | 13 | |
| 380 | 10 | |
| 268 | 9 | G268S, |
| 377 | 9 | |
| 353 | 4 | T353I, |
| 907 | 14 |