SCN5A Variant A110T

Summary of observed carriers, functional annotations, and structural context for SCN5A A110T. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

17%

1/15 effective observations

Estimated BrS1 penetrance

10%

1/15 effective observations

Total carriers

5

0 BrS1 · 1 LQT3 · 4 unaffected

A110T is present in 4 alleles in gnomAD. This residue resides in a Mild_Hotspot region for Brugada syndrome and a Mild_Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 1 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 (%)
-3.54 1 -1.09 0.953 14 19

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
23631430 2013 1 1 0 0
Literature, cohort, and gnomAD – 5 4 1 0 –
Variant features alone – 15 14 0 1 – –

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)
23631430 2013

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 A110T.
Neighbour residue Distance (Å) Observed variants
95 15 V95I, V95L,
96 14
97 14
98 13
99 13
100 12
101 11 T101I,
102 11
103 10
104 9 R104W, R104G, R104Q,
105 8
106 8 S106T,
107 7
108 5
109 4 N109K,
110 0 A110T,
111 4
112 5 Y112C,
113 7 V113I, V113A,
114 8
115 8 S115G,
116 9
117 10
118 11
119 11 P119L, P119S,
120 12
121 13 R121W, R121Q,
122 13
123 14 A123V, A123G,
124 14 A124D,
125 15 V125L,