SCN5A Variant A572V

Summary of observed carriers, functional annotations, and structural context for SCN5A A572V. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

1%

1/78 effective observations

Estimated BrS1 penetrance

1%

0/78 effective observations

Total carriers

68

0 BrS1 · 1 LQT3 · 67 unaffected

A572V is present in 67 alleles in gnomAD. This residue resides in a Non_Hotspot region for Brugada syndrome and a Non_Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 0 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 (%)
-0.37 0 -0.64 0.496 3 4

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
22360817 2012 1 1 0 0
19716085 2009 2 2 0 0
29214556 2017 1 0 0 1 SCD
Literature, cohort, and gnomAD – 68 67 1 0 –
Variant features alone – 15 15 0 0 – –

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)
22360817 2012
19716085 2009
29214556 2017

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 A572V.
Neighbour residue Distance (Å) Observed variants
557 15 H557L, H557Q, H557Q, H557Y,
558 14 H558R,
559 14 T559I, T559R,
560 13
561 13
562 12
563 11 V563G,
564 11
565 10
566 9
567 8 L567Q,
568 8 R568H, R568C,
569 7 c.1705dupC, R569W, R569Q,
570 5 T570N,
571 4 S571I,
572 0 A572S, A572D, A572V, A572F,
573 4 Q573X, Q573E, Q573R,
574 5 c.1721delG, G574E,
575 7
576 8
577 8 S577N,
578 9 P578R, P578T,
579 10 G579R, G579R,
580 11
581 11 S581L,
582 12
583 13 P583L,
584 13 G584R,
585 14
586 14 A586G, A586T, p.586_587delAL,
587 15