SCN5A Variant A993T

Summary of observed carriers, functional annotations, and structural context for SCN5A A993T. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

25%

2/15 effective observations

Estimated BrS1 penetrance

0%

0/15 effective observations

Total carriers

5

0 BrS1 · 2 LQT3 · 3 unaffected

A993T is present in 3 alleles 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 0 individuals for LQT3.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density BrS (%) Penetrance Density LQT3 (%)
-0.09 0.001 -0.02 0.263 1 13

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
27287068 2016 2 2 0 0
Literature, cohort, and gnomAD – 5 3 2 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)
27287068 2016 Oocytes 175

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 A993T.
Neighbour residue Distance (Å) Observed variants
978 15
979 14 D979H,
980 14
981 13 C981F,
982 13 C982R,
983 12 G983D,
984 11
985 11
986 10 R986L, R986W, R986Q,
987 9
988 8 R988W, R988Q,
989 8
990 7
991 5 K991E, K991T,
992 4
993 0 A993T, A993S,
994 4 A994V, A994T,
995 5 L995F,
996 7 A996T,
997 8 A997S, A997T, A997D
998 8
999 9 G999D,
1000 10 Q1000X, p.Gln1000del, Q1000L,
1001 11
1002 11 c.3005-3012delCCAGCTGG, P1002S,
1003 12
1004 13 C1004R,
1005 13 I1005V, I1005T,
1006 14 A1006S,
1007 14 T1007I, T1007N,
1008 15 P1008S,