SCN5A Variant c.4813+3_4813+6dupGGGT

Summary of observed carriers, functional annotations, and structural context for SCN5A c.4813+3_4813+6dupGGGT. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

0%

0/42 effective observations

Estimated BrS1 penetrance

70%

29/42 effective observations

Total carriers

32

26 BrS1 · 0 LQT3 · 6 unaffected

c.4813+3_4813+6dupGGGT 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 3 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 49 1

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
28781330 2017 32 0 26 0
Literature, cohort, and gnomAD – 32 6 0 26 –
Variant features alone – 15 12 0 3 – –

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)
28781330 2017

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.4813+3_4813+6dupGGGT.
Neighbour residue Distance (Å) Observed variants
1569 13 A1569P,
1567 15 F1567L, F1567L, F1567L,
1566 15
1568 10
1602 5
1601 7 L1601H,
1609 6 S1609W, S1609L,
1562 15
1608 5
1613 10 Q1613L, Q1613H, Q1613H,
1600 10
1571 14 F1571C,
1612 13
1615 14 Y1615X,
1572 13
1564 11
1599 10
1626 12 R1626C, R1626H, R1626P, R1626L
1603 6 I1603F,
1625 13
1606 4 T1606I,
1610 7 D1610G,
1596 15 F1596I, F1596C,
1597 13 V1597M,
1620 13 T1620K, T1620M,
1565 10 L1565M,
1614 14
1619 10 P1619Q, P1619L, c.4856delC,
1605 0 c.4813+2_4813+5dupTGGG, c.4813+3_4813+6dupGGGT, c.4813+5insTGGG, G1605C, G1605D,
1611 11 I1611V,
1563 15
1616 9
1607 6
1617 7 p.F1617del,
1604 4 c.4810+3_4810+6dupGGGT, V1604M,
1622 8
1618 10
1621 13
1598 11 V1598A,
1561 12
1623 12 c.4867delC, R1623X, R1623Q, R1623L,