SCN5A Variant P1506T

Summary of observed carriers, functional annotations, and structural context for SCN5A P1506T. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

22%

1/11 effective observations

Estimated BrS1 penetrance

45%

4/11 effective observations

Total carriers

1

1 BrS1 · 0 LQT3 · 0 unaffected

P1506T has not been reported in gnomAD. This residue resides in a Hotspot region for Brugada syndrome and a Mild_Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 3 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 (%)
-7.36 0.999 -3.21 0.934 55 30

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
23321620 2013 1 0 1 0
Literature, cohort, and gnomAD 1 0 0 1
Variant features alone 15 11 1 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)
23321620 2013

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 P1506T.
Neighbour residue Distance (Å) Observed variants
1850 8 C1850S, C1850S,
1803 11
1794 10
1849 10 H1849R,
1806 8 p.Thr1806SerfsX27,
1853 13 I1853V,
1795 6 Y1795C, Y1795H, p.Y1795_E1796insD, Y1795N,
1801 13
1511 14
1802 8
1510 13
1504 8 K1504E,
1851 10 M1851I, M1851V, M1851I, M1851I,
1501 13 p.L1501_K1505del, L1501V,
1507 5 p.Q1507_P1509del,
1505 5 p.K1505_Q1507del, K1505N, K1505N,
1509 9 P1509T,
1808 11
1804 11
1807 6 c.5420dupA,
1798 7 W1798X,
1585 15 Y1585C,
1854 11
1797 12 I1797V,
1800 12
1793 13 M1793K,
1848 14
1817 14
1796 10
1799 8
1788 14 c.5361_5364delTGAG,
1500 15 p.K1500del,
1791 12
1852 14 D1852V,
1792 11 D1792Y, D1792N, D1792V,
1508 7
1502 12 G1502A, G1502S,
1805 6
1809 12 I1809M
1506 0 P1506T, P1506S,
1503 10 S1503Y,