SCN5A Variant c.4719C>T

Summary of observed carriers, functional annotations, and structural context for SCN5A c.4719C>T. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

2%

0/12 effective observations

Estimated BrS1 penetrance

64%

7/12 effective observations

Total carriers

2

2 BrS1 · 0 LQT3 · 0 unaffected

c.4719C>T has not been reported in gnomAD. This residue resides in a Hotspot region for Brugada syndrome and a Non_Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 5 individuals for Brugada syndrome and 0 individuals for LQT3.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density BrS (%) Penetrance Density LQT3 (%)
NA NA NA None 86 0

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
21273195 2011 2 0 2 0
23425522 2013 2 0 2 0
27668095 2016 2 0 0 2 first degree heart block
Literature, cohort, and gnomAD – 2 0 0 2 –
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.

Published electrophysiology measurements.
PubMed ID Year Cell Type Peak Current (% WT) V1/2 Activation (mV) V1/2 Inactivation (mV) Late/Persistent Current (% WT)
21273195 2011
23425522 2013
27668095 2016

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 c.4719C>T.
Neighbour residue Distance (Å) Observed variants
1569 9 A1569P,
1525 9 V1525M, V1525A,
1524 10 I1524T,
1586 9
1567 11 F1567L, F1567L, F1567L,
1536 13
1538 10
1531 9
1566 13
1635 14
1568 10
1587 13 F1587V,
1602 13
1534 6
1601 15 L1601H,
1522 13
1575 4 C1575S, C1575S,
1600 12
1571 5 F1571C,
1523 15 D1523N,
1521 11 I1521T, I1521K,
1527 12 K1527R,
1572 6
1570 7 p.I1570dup, p.1570_F1571insI, I1570V,
1529 12
1599 9
1526 13 T1526P,
1583 15 R1583C, R1583H,
1580 11
1630 14 I1630R, I1630V,
1532 12 V1532I, V1532F,
1626 13 R1626P, R1626H, R1626L, R1626C,
1603 14 I1603F,
1625 14
1576 7
1596 10 F1596I, F1596C,
1628 14
1589 12
1632 10 R1632H, R1632C, R1632L,
1539 14 C1539F, C1539Y,
1597 12 V1597M,
1530 7
1573 5
1535 9
1537 9
1594 13 F1594S,
1581 11 A1581S,
1591 13 W1591X,
1593 12 I1593M,
1595 7
1629 9 R1629G, R1629X, R1629Q,
1574 0 c.4719C>T, E1574K,
1533 10 T1533I,
1541 13
1592 8
1578 5 c.4732_4733dupAA,
1540 14
1528 15
1631 15 G1631D,
1590 14
1582 11 L1582P,
1579 9 L1579fsX53,
1598 10 V1598A,
1577 6