SCN5A Variant T101I

Summary of observed carriers, functional annotations, and structural context for SCN5A T101I. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

16%

0/11 effective observations

Estimated BrS1 penetrance

13%

1/11 effective observations

Total carriers

1

0 BrS1 · 0 LQT3 · 1 unaffected

T101I is present in 1 alleles in gnomAD. This residue resides in a 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 (%)
-4.05 0.976 -0.16 0.838 11 22

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
29907895 2018 1 0 0 1 SIDS
Literature, cohort, and gnomAD – 1 1 0 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)
29907895 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 T101I.
Neighbour residue Distance (Å) Observed variants
86 15 F86L, F86L, F86L,
87 14 Y87C,
88 14 S88G,
89 13
90 13 p.Q90WfsX14,
91 12
92 11 c.274-24C>T, T92I,
93 11 F93S,
94 10 I94V, I94S,
95 9 V95I, V95L, V95L,
96 8
97 8
98 7
99 5
100 4
101 0 T101I,
102 4
103 5
104 7 R104G, R104W, R104Q,
105 8
106 8 S106T,
107 9
108 10
109 11 N109K, N109K,
110 11 A110T,
111 12
112 13 Y112C,
113 13 V113I, V113A,
114 14
115 14 S115G
116 15