SCN5A Variant G351C
Summary of observed carriers, functional annotations, and structural context for SCN5A G351C. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
5%
0/11 effective observations
Estimated BrS1 penetrance
54%
5/11 effective observations
Total carriers
1
1 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 (%) |
|---|---|---|---|---|---|
| -7.79 | 1 | -3.79 | 0.973 | 70 | 1 |
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 |
|---|---|---|---|---|---|---|---|
| 29325976 | 2018 | 1 | 0 | 1 | 0 | ||
| Literature, cohort, and gnomAD | – | 1 | 0 | 0 | 1 | – | |
| Variant features alone | – | 15 | 11 | 0 | 4 | – | – |
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) |
|---|---|---|---|---|---|---|
| 29325976 | 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 | 12 | |
| 277 | 9 | |
| 901 | 13 | S901L, E901K, |
| 276 | 10 | L276P, L276Q, |
| 363 | 11 | |
| 348 | 6 | P348A, |
| 360 | 8 | |
| 279 | 12 | |
| 355 | 11 | F355I, F355C, |
| 1549 | 15 | |
| 278 | 14 | H278D, H278R, |
| 356 | 10 | D356N, |
| 361 | 12 | |
| 904 | 8 | W904X, |
| 343 | 14 | |
| 376 | 12 | R376H, R376C, |
| 871 | 13 | |
| 354 | 7 | |
| 909 | 14 | |
| 902 | 15 | |
| 349 | 7 | D349N, |
| 1550 | 13 | |
| 357 | 11 | |
| 911 | 13 | G911E, |
| 272 | 15 | |
| 274 | 12 | G274C, |
| 273 | 15 | |
| 325 | 13 | L325R, |
| 900 | 12 | |
| 324 | 14 | |
| 321 | 13 | S321Y, |
| 872 | 13 | D872N, |
| 345 | 9 | |
| 916 | 14 | |
| 275 | 14 | N275K, N275K, |
| 912 | 10 | Q912R, |
| 323 | 13 | |
| 347 | 4 | |
| 906 | 14 | |
| 351 | 0 | G351C, G351V, G351S, G351D, |
| 910 | 15 | S910L, |
| 350 | 5 | H350Q, H350Q, |
| 903 | 12 | p.M903CfsX29, |
| 367 | 13 | R367L, R367C, R367H, |
| 346 | 6 | E346K, E346G, E346D, E346D, E346X, |
| 359 | 12 | p.A359PfsX12, A359T, |
| 344 | 12 | A344S, |
| 381 | 15 | c.1140+1G>A, c.1141-3C>A, |
| 322 | 11 | |
| 905 | 12 | |
| 352 | 4 | Y352C, |
| 915 | 15 | C915R, |
| 380 | 12 | |
| 377 | 12 | |
| 908 | 10 | |
| 353 | 5 | T353I, |
| 907 | 10 |