SCN5A Variant G514C

Summary of observed carriers, functional annotations, and structural context for SCN5A G514C. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

4%

0/12 effective observations

Estimated BrS1 penetrance

43%

5/12 effective observations

Total carriers

2

2 BrS1 · 0 LQT3 · 0 unaffected

G514C has not been reported in gnomAD. This residue resides in a Hotspot region for Brugada syndrome and a Non_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 (%)
-2.06 0.994 1.23 0.618 56 0

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
11234013 2001 5 0 0 5 Conduction disease
22885917 2012 2 0 2 0
19251209 2009 1 0 1 0
30059973 2018 2 2 0 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)
11234013 2001 HEK-tSA201 136 10.1 6.9
22885917 2012
25501501 2015
19251209 2009
16877553 2007 HEK
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 G514C.
Neighbour residue Distance (Å) Observed variants
499 15
500 14 E500K,
501 14 D501G,
502 13
503 13 P503S,
504 12 R504T,
505 11 A505E,
506 11 M506K,
507 10 p.N507_L515dup,
508 9
509 8
510 8
511 7
512 5 T512I,
513 4 R513H, R513C, R513P, c.1537delC,
514 0 G514C,
515 4
516 5
517 7 R517S, R517S,
518 8
519 8 S519F,
520 9 M520R, M520V,
521 10 K521E, c.1562delA,
522 11 P522S,
523 11 R523S, R523H, R523C,
524 12 c.1570_1571insG, S524Y,
525 13 S525G,
526 13 R526C, R526H,
527 14 G527R, G527R,
528 14 S528R, S528R, S528R,
529 15