SCN5A Variant L1772V
Summary of observed carriers, functional annotations, and structural context for SCN5A L1772V. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
57%
3/11 effective observations
Estimated BrS1 penetrance
10%
1/11 effective observations
Total carriers
1
0 BrS1 · 1 LQT3 · 0 unaffected
Variant features alone are equivalent to phenotyping 1 individuals for Brugada syndrome and 2 individuals for LQT3.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
|---|---|---|---|---|---|
| -2.78 | 0.999 | 0.88 | 0.874 | 9 | 65 |
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 |
|---|---|---|---|---|---|---|---|
| 19996378 | 2010 | 1 | 1 | 0 | 0 | ||
| Literature, cohort, and gnomAD | – | 1 | 0 | 1 | 0 | – | |
| Variant features alone | – | 15 | 12 | 2 | 1 | – | – |
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) |
|---|---|---|---|---|---|---|
| 19996378 | 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 |
|---|---|---|
| 403 | 11 | |
| 414 | 10 | M414V, |
| 939 | 10 | L939F, |
| 404 | 12 | L404V, L404Q, |
| 937 | 15 | |
| 1778 | 11 | |
| 1773 | 5 | |
| 1765 | 10 | |
| 249 | 15 | K249X, |
| 943 | 15 | S943N, |
| 1653 | 10 | |
| 1472 | 13 | p.N1472del, N1472S, |
| 1771 | 5 | I1771T, |
| 401 | 14 | S401P, |
| 1652 | 12 | M1652T, M1652R, |
| 1777 | 10 | V1777M, V1777L, V1777L, |
| 1764 | 13 | c.5290delG, V1764F, |
| 250 | 14 | |
| 409 | 6 | L409V, L409P, |
| 928 | 14 | L928P, |
| 1650 | 10 | L1650F, |
| 1656 | 13 | |
| 417 | 12 | |
| 1477 | 11 | K1477N, K1477N, |
| 933 | 13 | |
| 1471 | 11 | |
| 246 | 14 | |
| 935 | 10 | L935P, |
| 1779 | 11 | T1779M, |
| 412 | 10 | V412D, |
| 1470 | 7 | |
| 1466 | 9 | c.4396_4397insG, |
| 1478 | 15 | K1478E, |
| 1776 | 7 | |
| 1767 | 10 | Y1767C, |
| 1660 | 14 | I1660V, I1660S, |
| 1654 | 14 | |
| 1648 | 14 | |
| 1769 | 5 | |
| 402 | 13 | F402L, F402L, F402L, |
| 1766 | 11 | M1766L, M1766V, M1766L, M1766T, |
| 415 | 12 | A415T, |
| 1649 | 10 | A1649V, |
| 1768 | 6 | I1768V, |
| 940 | 14 | S940N, |
| 1774 | 7 | N1774D, c.5321_5324dupACTT, |
| 1473 | 9 | F1473S, F1473C, |
| 1468 | 13 | V1468F, V1468A, |
| 405 | 10 | |
| 1657 | 11 | |
| 1474 | 10 | |
| 938 | 14 | |
| 1781 | 15 | E1781G, E1781D, E1781D |
| 1772 | 0 | L1772V, |
| 1645 | 15 | T1645M, |
| 1323 | 15 | V1323G, |
| 410 | 5 | A410V, |
| 1780 | 13 | E1780G, |
| 1770 | 7 | I1770V, |
| 929 | 15 | |
| 416 | 14 | Y416C, |
| 413 | 8 | A413T, A413E, |
| 408 | 10 | |
| 253 | 14 | |
| 407 | 8 | |
| 1326 | 15 | A1326S, |
| 936 | 10 | |
| 1763 | 14 | V1763M, V1763L, V1763L, |
| 1467 | 10 | |
| 1476 | 15 | Q1476X, Q1476R, |
| 1775 | 6 | F1775V, p.F1775LfsX15, |
| 1475 | 15 | p.Q1475NfsX6, Q1475L, |
| 1469 | 10 | I1469V, |
| 406 | 7 | N406S, N406K, N406K, |
| 411 | 9 | V411M, |
| 932 | 11 | |
| 1647 | 14 | |
| 400 | 15 | G400R, G400R, G400E, G400A, |
| 1646 | 11 | |
| 1463 | 14 | N1463Y, |