SCN5A Variant N927S
Summary of observed carriers, functional annotations, and structural context for SCN5A N927S. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
4%
0/14 effective observations
Estimated BrS1 penetrance
54%
7/14 effective observations
Total carriers
4
4 BrS1 · 0 LQT3 · 0 unaffected
Variant features alone are equivalent to phenotyping 3 individuals for Brugada syndrome and 0 individuals for LQT3.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
|---|---|---|---|---|---|
| -4.3 | 0 | 1.87 | 0.805 | 48 | 5 |
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 |
|---|---|---|---|---|---|---|---|
| 16764707 | 2006 | 1 | 0 | 1 | 0 | ||
| 21273195 | 2011 | 4 | 0 | 4 | 0 | ||
| 20129283 | 2010 | 1 | 0 | 1 | 0 | ||
| 20129283 | 2010 | 1 | 0 | 1 | 0 | ||
| 29325976 | 2018 | 2 | 0 | 2 | 0 | ||
| 30059973 | 2018 | 1 | 1 | 0 | 0 | ||
| Literature, cohort, and gnomAD | – | 4 | 0 | 0 | 4 | – | |
| Variant features alone | – | 15 | 12 | 0 | 3 | – | – |
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 |
|---|---|---|
| 891 | 11 | I891N, I891T, |
| 890 | 14 | I890T, |
| 919 | 12 | |
| 896 | 7 | C896S, C896S, |
| 404 | 13 | L404V, L404Q, |
| 937 | 15 | |
| 895 | 6 | L895F, |
| 1417 | 15 | |
| 842 | 13 | |
| 894 | 8 | I894M, |
| 247 | 13 | V247L, V247L, |
| 1455 | 14 | |
| 254 | 14 | |
| 372 | 12 | |
| 401 | 13 | S401P, |
| 926 | 4 | |
| 371 | 12 | Q371E, |
| 250 | 13 | |
| 409 | 10 | L409V, L409P, |
| 928 | 4 | L928P, |
| 925 | 8 | I925F, |
| 366 | 12 | |
| 934 | 11 | |
| 1458 | 12 | S1458Y, |
| 933 | 10 | |
| 246 | 13 | |
| 935 | 10 | L935P, |
| 412 | 11 | V412D, |
| 897 | 7 | G897R, G897R, G897E, |
| 924 | 7 | V924I, |
| 927 | 0 | N927S, N927K, N927K, |
| 1466 | 15 | c.4396_4397insG, |
| 369 | 12 | M369K, |
| 845 | 14 | c.2533delG, |
| 1418 | 12 | |
| 892 | 11 | F892I, |
| 373 | 15 | |
| 1768 | 14 | I1768V |
| 849 | 11 | |
| 898 | 11 | |
| 893 | 12 | R893C, R893H, |
| 921 | 11 | |
| 922 | 8 | V922I, |
| 405 | 9 | |
| 1462 | 14 | |
| 920 | 11 | |
| 843 | 14 | T843A, |
| 900 | 15 | |
| 930 | 7 | c.2787+17_2787+18insACACACACACACACACACACACA, c.2788-6C>T, |
| 1459 | 10 | c.4376_4379delTCTT, |
| 918 | 14 | |
| 1454 | 13 | |
| 410 | 14 | A410V, |
| 242 | 15 | A242D, |
| 929 | 7 | |
| 413 | 14 | A413T, A413E, |
| 408 | 9 | |
| 847 | 14 | |
| 407 | 14 | |
| 846 | 10 | L846R, |
| 367 | 15 | R367C, R367H, R367L, |
| 936 | 13 | |
| 1416 | 15 | c.4245+1G>A, c.4245+1G>C, c.4245+2T>A, A1416E, A1416G, |
| 853 | 12 | |
| 370 | 9 | T370M, |
| 923 | 5 | |
| 406 | 12 | N406S, N406K, N406K, |
| 899 | 10 | |
| 850 | 12 | V850M, c.2549_2550insTG, |
| 411 | 14 | V411M, |
| 243 | 12 | |
| 932 | 6 | |
| 931 | 5 | |
| 1463 | 12 | N1463Y, |