SCN5A Variant D1714G

Summary of observed carriers, functional annotations, and structural context for SCN5A D1714G. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

3%

0/11 effective observations

Estimated BrS1 penetrance

59%

6/11 effective observations

Total carriers

1

1 BrS1 · 0 LQT3 · 0 unaffected

D1714G 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 (%)
-5.95 1 -3.31 0.958 82 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
16266370 2005 1 0 1 0
21273195 2011 1 0 1 0
19251209 2009 1 0 1 0
20129283 2010 1 0 1 0
Literature, cohort, and gnomAD 1 0 0 1
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)
16266370 2005 HEK 21 1.9 1.9
21273195 2011
19251209 2009
20390067 2010
16266366 2005
20129283 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.

Previously observed variants near D1714G.
Neighbour residue Distance (Å) Observed variants
1417 10
1406 15 G1406R, G1406R, G1406E,
1715 4
1687 10
1745 14
1756 12 I1756V
1711 9 c.5131delG,
1723 14 T1723N,
1707 11
1398 11 V1398M,
1411 9
1407 13
1704 15 L1704H,
1410 10
1706 12 Q1706H, Q1706H,
1716 7 p.L1716SfsX71,
1714 0 D1714G,
376 14 R376C, R376H,
1688 12
1423 9 D1423H,
1692 15
1744 14 S1744I,
1721 10
1753 13 T1753A,
1422 11 M1422R,
1418 12
373 13
1712 6 G1712S, G1712C,
379 14
1703 13
898 14
1412 13 L1412F,
1719 9
1408 13 G1408R, G1408R,
1709 14 p.T1709del, T1709R, T1709M,
1420 6 G1420R, G1420D, G1420V, G1420P,
1360 14 F1360C,
1755 15
1401 12
1425 14
1399 9
1713 7
1427 14 A1427S, A1427E,
1424 9 I1424V,
1748 12 p.G1748del, G1748D,
1409 14 Y1409C, Y1409X,
1400 8 V1400I,
1421 10
1718 6 S1718R, S1718R, S1718R,
374 15 W374G,
1717 5 L1717P,
1751 14
1416 12 c.4245+1G>A, c.4245+1G>C, c.4245+2T>A, A1416E, A1416G,
1760 15
1752 10
1722 14 N1722D,
1686 8
1749 12 I1749N,
375 11
1710 11 S1710L,
1720 10 c.5157delC,
1415 11
1685 11
1419 7 K1419E,
1414 6 Q1414H, Q1414H,
1402 14
1413 10