SCN5A Variant M135T

Summary of observed carriers, functional annotations, and structural context for SCN5A M135T. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

3%

0/10 effective observations

Estimated BrS1 penetrance

18%

1/10 effective observations

Total carriers

0

0 BrS1 · 0 LQT3 · 0 unaffected

M135T has not been reported in gnomAD. This residue resides in a Mild_Hotspot region for Brugada syndrome and a Non_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 (%)
NA NA NA 0.595 21 0

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 0 1 – –

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 M135T.
Neighbour residue Distance (Å) Observed variants
234 14 P234S
142 11
171 13
136 5 L136P,
168 14
233 14
229 12
141 11 I141V, I141N,
129 11
135 0 M135V,
167 14
128 12 c.381dupT,
137 8 I137V,
225 14 R225W, R225Q,
231 11 c.692_693delCA,
127 12
131 5
232 9 V232I, V232F,
230 15 I230V, I230T, I230M,
133 8
139 7 p.I137_C139dup,
132 5 c.393-5C>A,
130 8
228 12 K228R,
138 7 M138I, M138I, M138I,
134 5 N134S,
140 10
143 13