SCN5A Variant T1723N

Summary of observed carriers, functional annotations, and structural context for SCN5A T1723N. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

31%

2/12 effective observations

Estimated BrS1 penetrance

13%

1/12 effective observations

Total carriers

2

0 BrS1 · 1 LQT3 · 1 unaffected

T1723N is present in 1 alleles in gnomAD. This residue resides in a Mild_Hotspot region for Brugada syndrome and a Mild_Hotspot region for LQT3.

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

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density BrS (%) Penetrance Density LQT3 (%)
-1.58 0.776 -0.09 0.549 19 29

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
19716085 2009 1 1 0 0
Literature, cohort, and gnomAD 2 1 1 0
Variant features alone 15 13 1 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)
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 T1723N.
Neighbour residue Distance (Å) Observed variants
1403 11
1746 12 A1746T, A1746V,
1724 4
1406 12 G1406R, G1406E, G1406R,
1715 14
1361 14
1726 9
739 13
1745 9
1397 8 c.4189delT, c.4190delA,
1743 11 G1743R, G1743E, G1743R,
1723 0 T1723N,
1725 5 P1725L,
1398 10 V1398M,
1411 14
1407 10
1410 12
1747 14 V1747M,
1714 14 D1714G,
1396 12
1404 11
1744 11 S1744I,
1721 7
1742 13
1727 11
1719 11
1408 13 G1408R, G1408R,
1731 14
1728 9 C1728Y, C1728R, C1728W,
1360 13 F1360C,
1401 9
1399 6
1748 13 G1748D, p.G1748del,
738 14
1683 14
740 15 p.N740del,
1400 10 V1400I,
1718 9 S1718R, S1718R, S1718R,
1717 12 L1717P,
1682 15
1722 5 N1722D,
1686 15
1749 12 I1749N,
1729 13 D1729N,
1720 11 c.5157delC
1685 13
1402 14