SCN5A Variant P1014S

Summary of observed carriers, functional annotations, and structural context for SCN5A P1014S. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

6%

0/12 effective observations

Estimated BrS1 penetrance

43%

5/12 effective observations

Total carriers

2

2 BrS1 · 0 LQT3 · 0 unaffected

P1014S 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 0 individuals for LQT3.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density BrS (%) Penetrance Density LQT3 (%)
0.2 0.09 0.07 0.447 54 13

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
29325976 2018 1 0 1 0
29574140 2018 1 0 1 0
Literature, cohort, and gnomAD – 2 0 0 2 –
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)
32533946 2020 HEK 121 -9.8 -0.4
29325976 2018
29574140 2018

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 P1014S.
Neighbour residue Distance (Å) Observed variants
999 15 G999D,
1000 14 Q1000X, p.Gln1000del, Q1000L,
1001 14
1002 13 c.3005-3012delCCAGCTGG, P1002S,
1003 13
1004 12 C1004R,
1005 11 I1005V, I1005T,
1006 11 A1006S,
1007 10 T1007I, T1007N,
1008 9 P1008S,
1009 8
1010 8
1011 7 P1011S, P1011L,
1012 5
1013 4
1014 0 P1014S,
1015 4 E1015K, p.G1015DfsX14,
1016 5 T1016M, c.3045_3046delGA,
1017 7
1018 8 K1018E,
1019 8
1020 9
1021 10 P1021S,
1022 11
1023 11 R1023P, R1023H, R1023C,
1024 12 K1024R,
1025 13 E1025A,
1026 13
1027 14 R1027P, R1027W, R1027Q,
1028 14
1029 15 E1029K,