SCN5A Variant L935P
Summary of observed carriers, functional annotations, and structural context for SCN5A L935P. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
4%
0/11 effective observations
Estimated BrS1 penetrance
61%
6/11 effective observations
Total carriers
1
1 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 (%) |
|---|---|---|---|---|---|
| -6.24 | 1 | -4.76 | 0.996 | 83 | 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 |
|---|---|---|---|---|---|---|---|
| 20129283 | 2010 | 1 | 0 | 1 | 0 | ||
| Literature, cohort, and gnomAD | – | 1 | 0 | 0 | 1 | – | |
| 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.
| PubMed ID | Year | Cell Type | Peak Current (% WT) | V1/2 Activation (mV) | V1/2 Inactivation (mV) | Late/Persistent Current (% WT) |
|---|---|---|---|---|---|---|
| 20129283 | 2010 |
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 |
|---|---|---|
| 414 | 13 | M414V, |
| 939 | 7 | L939F, |
| 896 | 14 | C896S, |
| 937 | 7 | |
| 895 | 13 | L895F, |
| 1773 | 14 | |
| 1765 | 10 | |
| 839 | 12 | L839P, |
| 842 | 11 | |
| 943 | 13 | S943N, |
| 1457 | 13 | |
| 1455 | 13 | |
| 1771 | 13 | I1771T, |
| 1461 | 11 | T1461S, |
| 926 | 12 | |
| 1764 | 14 | c.5290delG, V1764F, |
| 409 | 7 | L409V, L409P, |
| 928 | 11 | L928P, |
| 417 | 12 | |
| 934 | 5 | |
| 1458 | 11 | S1458Y, |
| 933 | 7 | |
| 1471 | 12 | |
| 246 | 13 | |
| 935 | 0 | L935P, |
| 412 | 9 | V412D, |
| 1470 | 9 | |
| 1464 | 9 | c.4389_4396delCCTCTTTA, L1464P, |
| 927 | 10 | N927K, N927S, |
| 1466 | 7 | c.4396_4397insG, |
| 1776 | 15 | |
| 1769 | 12 | |
| 1766 | 15 | M1766L, M1766V, M1766T, |
| 415 | 13 | A415T, |
| 1768 | 10 | I1768V, |
| 940 | 10 | S940N, |
| 1468 | 11 | V1468F, V1468A, |
| 405 | 11 | |
| 1462 | 10 | |
| 938 | 6 | |
| 840 | 15 | |
| 942 | 10 | |
| 420 | 14 | |
| 843 | 13 | T843A, |
| 1456 | 15 | |
| 930 | 9 | c.2787+17_2787+18insACACACACACACACACACACACA, c.2788-6C>T, |
| 1459 | 9 | c.4376_4379delTCTT, |
| 1772 | 10 | L1772V, |
| 1460 | 10 | F1460L, |
| 239 | 13 | I239V , I239V, |
| 1454 | 15 | |
| 410 | 10 | A410V, |
| 242 | 13 | A242D, |
| 929 | 10 | |
| 416 | 10 | Y416C, |
| 413 | 8 | A413E, A413T, |
| 408 | 11 | |
| 941 | 11 | S941F, S941N, |
| 407 | 14 | |
| 1337 | 15 | |
| 846 | 13 | L846R, |
| 936 | 5 | |
| 838 | 13 | |
| 1465 | 11 | p.F1465_L1480dup, |
| 1760 | 14 | |
| 1467 | 8 | |
| 1775 | 15 | p.F1775LfsX15, F1775V, |
| 1761 | 14 | L1761H, c.5280delG, L1761F, |
| 1469 | 11 | I1469V, |
| 406 | 10 | N406S, N406K, |
| 411 | 12 | V411M, |
| 243 | 14 | |
| 932 | 5 | |
| 832 | 15 | |
| 835 | 14 | S835A, S835L, |
| 931 | 7 | |
| 1463 | 6 | N1463Y, |