SCN5A Variant P1011L

Summary of observed carriers, functional annotations, and structural context for SCN5A P1011L. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

0%

0/19 effective observations

Estimated BrS1 penetrance

7%

1/19 effective observations

Total carriers

9

0 BrS1 · 0 LQT3 · 9 unaffected

P1011L is present in 9 alleles in gnomAD. This residue resides in a Non_Hotspot region for Brugada syndrome and a Non_Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 1 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 (%)
-0.66 0.271 -1.63 0.74 4 6

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
24631775 2014 1 0 0 1 SIDS
Literature, cohort, and gnomAD – 9 9 0 0 –
Variant features alone – 15 14 0 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)
24631775 2014

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 P1011L.
Neighbour residue Distance (Å) Observed variants
996 15 A996T,
997 14 A997S, A997T, A997D
998 14
999 13 G999D,
1000 13 Q1000X, p.Gln1000del, Q1000L,
1001 12
1002 11 c.3005-3012delCCAGCTGG, P1002S,
1003 11
1004 10 C1004R,
1005 9 I1005V, I1005T,
1006 8 A1006S,
1007 8 T1007I, T1007N,
1008 7 P1008S,
1009 5
1010 4
1011 0 P1011S, P1011L,
1012 4
1013 5
1014 7 P1014S,
1015 8 E1015K, p.G1015DfsX14,
1016 8 T1016M, c.3045_3046delGA,
1017 9
1018 10 K1018E,
1019 11
1020 11
1021 12 P1021S,
1022 13
1023 13 R1023P, R1023H, R1023C,
1024 14 K1024R,
1025 14 E1025A,
1026 15