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

F1473C has not been reported in gnomAD. This residue resides in a Non_Hotspot region for Brugada syndrome and a Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 1 individuals for Brugada syndrome and 3 individuals for LQT3.

In silico predictors

Variant-level computational 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

Observed carriers by publication or cohort.
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.

Published electrophysiology measurements.
PubMed ID Year Cell Type Peak Current (% WT) V1/2 Activation (mV) V1/2 Inactivation (mV) Late/Persistent Current (% WT)
18060054 2007 HEK 100 -2.4 8.8 630
23277474 2013 hiPSC-CM 100 -0.6 10 1600
20197117 2010
19669871 2009
19716085 2009

Nearby variants

Neighbouring residues within 15 Ångström provide structural context. Variants listed in the right-most column have been observed clinically or in gnomAD.

Previously observed variants near F1473C.
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,