SCN5A Variant L212P

Summary of observed carriers, functional annotations, and structural context for SCN5A L212P. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

45%

2/11 effective observations

Estimated BrS1 penetrance

26%

2/11 effective observations

Total carriers

1

0 BrS1 · 1 LQT3 · 0 unaffected

L212P 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 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 (%)
-6.79 0.999 -0.24 0.975 41 39

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
16188595 2005 1 0 0 1 Atrial standstill
19716085 2009 1 1 0 0
30059973 2018 2 2 0 0
Literature, cohort, and gnomAD – 1 0 1 0 –
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)
20539757 2010
19716085 2009
16188595 2005 tsA201 120 -15.4 -9
20384651 2010 HEK 94 -14.6 -10.4
30059973 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 L212P.
Neighbour residue Distance (Å) Observed variants
203 13
208 10 E208K,
205 14 Y205X, c.612-2A>G,
156 14 W156R, W156X,
158 12 K158T,
859 13
206 10
216 8 S216L, S216X,
214 7
161 14 E161Q, E161K,
219 10 R219H, R219C, c.656_657insATTCA, p.R219HfsX11,
211 5
217 11
222 14 R222L, R222X, R222Q,
218 9
213 5
207 7
212 0 L212Q, L212P,
209 9 N209T, N209S,
215 9 p.L215CfsX10,
863 14
210 5 I210T,
220 13 T220I,
204 12 c.611+1G>A, c.611+3_611+4dupAA, A204V, A204T,
162 14 Y162C, Y162H,