SCN5A Variant G1712C

Summary of observed carriers, functional annotations, and structural context for SCN5A G1712C. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

5%

0/11 effective observations

Estimated BrS1 penetrance

57%

6/11 effective observations

Total carriers

1

1 BrS1 · 0 LQT3 · 0 unaffected

G1712C 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 (%)
-8.33 1 -3.96 0.967 74 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
28219873 2016 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)
28219873 2016 HEK 0

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 G1712C.
Neighbour residue Distance (Å) Observed variants
1702 13
901 15 E901K, S901L,
1417 10
1715 5
1687 8
1413 13
372 12
1756 11 I1756V,
371 12 Q371E,
1711 4 c.5131delG,
1707 7
1694 13
1411 14
1704 11 L1704H,
1410 14
1706 6 Q1706H, Q1706H,
1716 5 p.L1716SfsX71,
1714 6 D1714G,
376 10 R376C, R376H,
1688 11
897 14 G897R, G897R, G897E,
1423 12 D1423H,
1692 11
1721 13
1753 14 T1753A,
1422 13 M1422R,
1693 14
378 11
1418 11
373 9
1712 0 G1712S, G1712C,
379 10
1703 9
898 12
1759 14 S1759C
1719 11
1709 9 p.T1709del, T1709R, T1709M,
1420 8 G1420R, G1420D, G1420V, G1420P,
1755 12
1399 14
1713 5
1424 14 I1424V,
1748 14 p.G1748del, G1748D,
1708 10 T1708I,
1400 14 V1400I,
1421 12
1718 10 S1718R, S1718R, S1718R,
374 9 W374G,
1705 12
1689 13 D1689N,
1700 14
1717 8 L1717P,
367 14 R367C, R367H, R367L,
1751 13
1416 13 c.4245+1G>A, c.4245+1G>C, c.4245+2T>A, A1416E, A1416G,
1760 12
1752 9
1686 10
1749 15 I1749N,
375 6
1691 15
368 15
1710 7 S1710L,
380 14
1720 12 c.5157delC,
1415 13
377 13
1685 13
1419 6 K1419E,
1414 9 Q1414H, Q1414H,