SCN5A Variant N109K

Summary of observed carriers, functional annotations, and structural context for SCN5A N109K. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

11%

1/14 effective observations

Estimated BrS1 penetrance

40%

5/14 effective observations

Total carriers

4

3 BrS1 · 0 LQT3 · 1 unaffected

N109K is present in 1 alleles in gnomAD. This residue resides in a Non_Hotspot region for Brugada syndrome and a Mild_Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 2 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 (%)
-0.67 0.208 2.46 0.362 49 23

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
19843921 2009 1 0 1 0
21273195 2011 3 0 3 0
20129283 2010 1 0 1 0
Literature, cohort, and gnomAD – 4 1 0 3 –
Variant features alone – 15 12 1 2 – –

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)
20129283 2010
32533946 2020 HEK 120 -1.4 1.3
19843921 2009
21273195 2011

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 N109K.
Neighbour residue Distance (Å) Observed variants
94 15 I94V, I94S,
95 14 V95I, V95L,
96 14
97 13
98 13
99 12
100 11
101 11 T101I,
102 10
103 9
104 8 R104W, R104Q, R104G,
105 8
106 7 S106T,
107 5
108 4
109 0 N109K,
110 4 A110T
111 5
112 7 Y112C,
113 8 V113I, V113A,
114 8
115 9 S115G,
116 10
117 11
118 11
119 12 P119L, P119S,
120 13
121 13 R121Q, R121W,
122 14
123 14 A123V, A123G,
124 15 A124D,