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, |