SCN5A Variant M506L

Summary of observed carriers, functional annotations, and structural context for SCN5A M506L. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

22%

1/10 effective observations

Estimated BrS1 penetrance

8%

0/10 effective observations

Total carriers

0

0 BrS1 · 0 LQT3 · 0 unaffected

M506L has not been reported 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 0 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 (%)
NA NA NA 0.545 3 29

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
Literature, cohort, and gnomAD – 0 0 0 0 –
Variant features alone – 15 14 1 0 – –

Totals may differ from individual publications due to duplicate patients removed during curation.

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 M506L.
Neighbour residue Distance (Å) Observed variants
491 15 E491G,
492 14
493 14 R493K,
494 13
495 13
496 12 K496N, K496M, K496N,
497 11 S497C,
498 11
499 10
500 9 E500K,
501 8 D501G,
502 8
503 7 P503S,
504 5 R504T,
505 4 A505E,
506 0 M506K,
507 4 p.N507_L515dup,
508 5
509 7
510 8
511 8
512 9 T512I,
513 10 R513H, c.1537delC, R513P, R513C,
514 11 G514C,
515 11
516 12
517 13 R517S, R517S,
518 13
519 14 S519F,
520 14 M520V, M520R,
521 15 K521E, c.1562delA,