SCN5A Variant F1473C
Summary of observed carriers, functional annotations, and structural context for SCN5A F1473C. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
76%
5/12 effective observations
Estimated BrS1 penetrance
8%
1/12 effective observations
Total carriers
2
0 BrS1 · 2 LQT3 · 0 unaffected
Variant features alone are equivalent to phenotyping 1 individuals for Brugada syndrome and 3 individuals for LQT3.
In silico predictors
PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
---|---|---|---|---|---|
-7.66 | 0.998 | -5.87 | 0.979 | 2 | 90 |
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 |
---|---|---|---|---|---|---|---|
18060054 | 2007 | 1 | 1 | 0 | 0 | ||
23277474 | 2013 | 1 | 1 | 0 | 0 | ||
20197117 | 2010 | 2 | 1 | 0 | 1 | AV block | |
19669871 | 2009 | 1 | 1 | 0 | 0 | ||
19716085 | 2009 | 1 | 1 | 0 | 0 | ||
Literature, cohort, and gnomAD | – | 2 | 0 | 2 | 0 | – | |
Variant features alone | – | 15 | 11 | 3 | 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.
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 |
---|---|---|
1328 | 11 | V1328M, |
939 | 13 | L939F, |
1659 | 13 | |
1480 | 11 | c.4437+5G>A, c.4438-1C>T, |
1773 | 7 | |
1765 | 10 | |
943 | 14 | S943N, |
1653 | 12 | |
1472 | 5 | N1472S, p.N1472del, |
1771 | 10 | I1771T, |
1652 | 14 | M1652T, M1652R, |
1777 | 13 | V1777L, V1777L, V1777M, |
1320 | 12 | M1320I, M1320I, M1320I, |
1764 | 12 | c.5290delG, V1764F, |
409 | 15 | L409P, L409V, |
1333 | 13 | |
1656 | 10 | |
1477 | 6 | K1477N, K1477N, |
1471 | 8 | |
1762 | 11 | p.I1762del, I1762M, |
1470 | 6 | |
1466 | 10 | c.4396_4397insG, |
1478 | 10 | K1478E, |
1776 | 12 | |
944 | 15 | |
1767 | 11 | Y1767C, |
1660 | 11 | I1660S, I1660V, |
1329 | 10 | G1329S, |
1769 | 5 | |
1766 | 6 | M1766V, M1766L, M1766L, M1766T, |
1319 | 11 | G1319V, |
1768 | 9 | I1768V, |
1774 | 10 | c.5321_5324dupACTT, N1774D, |
1479 | 10 | |
1473 | 0 | F1473C, F1473S, |
1334 | 13 | I1334V, |
1468 | 9 | V1468A, V1468F, |
1663 | 14 | |
1657 | 11 | |
1474 | 7 | |
1324 | 10 | |
1481 | 13 | G1481R, G1481E, G1481R, G1481V, |
1327 | 9 | |
1330 | 9 | A1330T, A1330P, A1330D, |
1772 | 9 | L1772V, |
1321 | 14 | R1321K, |
1323 | 7 | V1323G, |
410 | 15 | A410V, |
1770 | 6 | I1770V, |
1482 | 14 | |
1322 | 7 | c.3963+2T>C, c.3963+4A>G, |
1326 | 6 | A1326S, |
1763 | 11 | V1763L, V1763L, V1763M, |
1332 | 14 | P1332Q, P1332L, |
1465 | 13 | p.F1465_L1480dup, |
1467 | 10 | |
1476 | 6 | Q1476X, Q1476R, |
1775 | 14 | F1775V, p.F1775LfsX15, |
1661 | 15 | G1661R, G1661E, G1661R, |
1331 | 13 | I1331V, |
1761 | 15 | L1761H, c.5280delG, L1761F, |
1655 | 14 | |
1475 | 8 | p.Q1475NfsX6, Q1475L, |
1469 | 6 | I1469V, |
406 | 14 | N406S, N406K, N406K, |
1325 | 9 | N1325S, |