SCN5A Variant M369K
Summary of observed carriers, functional annotations, and structural context for SCN5A M369K. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
9%
0/13 effective observations
Estimated BrS1 penetrance
62%
8/13 effective observations
Total carriers
3
3 BrS1 · 0 LQT3 · 0 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 (%) |
|---|---|---|---|---|---|
| -5.89 | 0.963 | -3.37 | 0.986 | 71 | 18 |
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 |
|---|---|---|---|---|---|---|---|
| 12106943 | 2002 | 1 | 0 | 1 | 0 | ||
| 16643399 | 2006 | 1 | 0 | 1 | 0 | ||
| 17404158 | 2007 | 1 | 0 | 1 | 0 | ||
| 26921764 | 2016 | 3 | 0 | 3 | 0 | ||
| 20129283 | 2010 | 1 | 0 | 1 | 0 | ||
| 30059973 | 2018 | 3 | 3 | 0 | 0 | ||
| Literature, cohort, and gnomAD | – | 3 | 0 | 0 | 3 | – | |
| 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.
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 |
|---|---|---|
| 403 | 10 | |
| 364 | 9 | |
| 363 | 11 | |
| 404 | 6 | L404V, L404Q, |
| 396 | 7 | V396L, V396A, |
| 355 | 14 | F355C, F355I, |
| 254 | 11 | |
| 372 | 10 | |
| 1771 | 14 | I1771T, |
| 401 | 4 | S401P, |
| 1764 | 15 | V1764F, c.5290delG, |
| 371 | 7 | Q371E, |
| 250 | 14 | |
| 409 | 14 | L409P, L409V, |
| 928 | 10 | L928P, |
| 1650 | 15 | L1650F, |
| 361 | 12 | |
| 260 | 9 | |
| 366 | 5 | |
| 365 | 6 | |
| 258 | 11 | V258A, |
| 897 | 12 | G897E, G897R, |
| 924 | 12 | V924I, |
| 927 | 12 | N927K, N927S, |
| 369 | 0 | M369K, |
| 1767 | 14 | Y1767C, |
| 402 | 9 | F402L, |
| 373 | 13 | |
| 1768 | 14 | I1768V, |
| 267 | 14 | |
| 262 | 12 | S262G, |
| 256 | 11 | |
| 399 | 10 | |
| 397 | 7 | I397V, I397T, I397F, |
| 405 | 7 | |
| 362 | 10 | |
| 261 | 7 | |
| 920 | 12 | |
| 1709 | 12 | p.T1709del, T1709M, T1709R, |
| 900 | 14 | |
| 392 | 12 | |
| 255 | 14 | |
| 395 | 11 | |
| 393 | 11 | |
| 394 | 13 | |
| 264 | 9 | |
| 259 | 13 | |
| 265 | 11 | A265V, |
| 408 | 11 | |
| 374 | 11 | W374G, |
| 253 | 12 | |
| 407 | 11 | |
| 367 | 9 | R367C, R367H, R367L, |
| 263 | 12 | V263I, |
| 370 | 5 | T370M, |
| 923 | 11 | |
| 406 | 10 | N406S, N406K, |
| 368 | 6 | |
| 899 | 11 | |
| 268 | 14 | G268S, |
| 377 | 13 | |
| 932 | 14 | |
| 398 | 11 | |
| 257 | 8 | |
| 400 | 5 | G400A, G400E, G400R, |