SCN5A Variant D501G

Summary of observed carriers, functional annotations, and structural context for SCN5A D501G. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

5%

0/11 effective observations

Estimated BrS1 penetrance

46%

5/11 effective observations

Total carriers

1

1 BrS1 · 0 LQT3 · 0 unaffected

D501G 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 4 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 (%)
-4.18 0.992 0.12 0.881 59 2

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
20129283 2010 1 0 1 0
29759671 2018 1 0 1 0
Literature, cohort, and gnomAD – 1 0 0 1 –
Variant features alone – 15 11 0 4 – –

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
20129283 2010
29759671 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 D501G.
Neighbour residue Distance (Å) Observed variants
486 15 T486A, T486S, T486S,
487 14
488 14
489 13
490 13 G490E, G490A,
491 12 E491G,
492 11
493 11 R493K,
494 10
495 9
496 8 K496M, K496N, K496N,
497 8 S497C,
498 7
499 5
500 4 E500K,
501 0 D501G,
502 4
503 5 P503S,
504 7 R504T,
505 8 A505E,
506 8 M506K,
507 9 p.N507_L515dup,
508 10
509 11
510 11
511 12
512 13 T512I,
513 13 R513C, c.1537delC, R513H, R513P,
514 14 G514C
515 14
516 15