SCN5A Variant L142H

Summary of observed carriers, functional annotations, and structural context for SCN5A L142H. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

4%

0/10 effective observations

Estimated BrS1 penetrance

15%

1/10 effective observations

Total carriers

0

0 BrS1 · 0 LQT3 · 0 unaffected

L142H 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 0.962 13 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 L142H.
Neighbour residue Distance (Å) Observed variants
848 11 I848F,
223 12 V223L,
231 11 c.692_693delCA,
149 12
147 11
164 11 F164L, F164L, F164L,
228 10 K228R,
138 6 M138I, M138I, M138I,
227 12 L227P,
171 15
143 5
137 9 I137V,
142 0
197 15
229 7
163 15 c.486delC,
851 11 c.2550_2551dupGT, F851L, p.F851CfsX19, c.2552_2553dupGT, F851L, F851L
852 13
222 14 R222X, R222Q, R222L,
224 14 L224F,
845 14 c.2533delG,
150 13
232 10 V232I, V232F,
133 14
132 15 c.393-5C>A,
160 14 p.V160fs,
134 13 N134S,
226 8 A226G, A226V,
144 7
855 14
230 11 I230V, I230T, I230M,
139 5 p.I137_C139dup,
148 10
884 15
146 7 V146M, V146A,
847 13
136 10 L136P,
168 12
233 12
141 5 I141V, I141N,
135 11 M135V,
167 13
225 10 R225W, R225Q,
151 15
844 12 L844RfsX3,
145 5
140 7