SCN5A Variant L1255M

Summary of observed carriers, functional annotations, and structural context for SCN5A L1255M. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

2%

0/11 effective observations

Estimated BrS1 penetrance

12%

1/11 effective observations

Total carriers

1

0 BrS1 · 0 LQT3 · 1 unaffected

L1255M is present in 1 alleles 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 (%)
-1.65 0.918 1.41 0.774 12 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 – 1 1 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 L1255M.
Neighbour residue Distance (Å) Observed variants
1253 8 E1253G,
1211 14
1267 12
1252 6
1262 11 G1262S,
1283 13 L1283M,
1280 13
1247 12 T1247I,
1282 14 S1282A,
1259 7
1257 8
1256 5
1250 10
1275 12 D1275N,
1255 0 L1255M,
1251 6 V1251M,
1248 12
1279 10 V1279I,
1258 5
1254 5
1207 14
1276 11
1278 14 I1278N,
1272 13
1266 11
1260 10 A1260D
1261 12
1249 10 V1249D,
1263 12