SCN5A Variant S1218T

Summary of observed carriers, functional annotations, and structural context for SCN5A S1218T. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

4%

0/11 effective observations

Estimated BrS1 penetrance

29%

3/11 effective observations

Total carriers

1

0 BrS1 · 0 LQT3 · 1 unaffected

S1218T 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 3 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 (%)
-2.93 0.995 -0.71 0.947 45 6

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 12 0 3 – –

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 S1218T.
Neighbour residue Distance (Å) Observed variants
1245 10 M1245I, M1245I, M1245I,
1218 0 S1218T, S1218I,
1281 15 c.3840+1G>A, V1281F,
1304 11 T1304M,
1217 4
1243 10 D1243N,
1216 6 L1216V,
1220 5 G1220E,
1673 11
1213 9
1210 12 F1210S,
1241 11
1309 9 R1309C, R1309H,
1226 14
1669 11
1221 5 A1221V,
1242 7
1219 4 S1219N,
1672 15 S1672Y
1313 14
1279 15 V1279I,
1239 9 L1239P,
1310 10
1306 7 R1306S, R1306H,
1244 13 K1244E,
1305 12
1246 6
1235 13
1282 13 S1282A,
1302 15 p.L1302Vfs18,
1247 12 T1247I,
1237 15 V1237F,
1307 9
1223 9 c.3667delG,
1697 14
1275 14 D1275N,
1222 6 p.L1222LfsX7, L1222R,
1215 6 I1215V,
1301 14
1214 7 M1214T,
1212 11 p.I1212del,
1253 14 E1253G,
1211 11
1311 14 L1311P,
1308 12 L1308F,
1250 10
1224 10
1670 13
1209 14 T1209R,
1240 12 E1240Q,
1248 14
1225 11 E1225K, G1225K,
1278 12 I1278N,
1238 11
1249 11 V1249D,
1303 9 R1303W, R1303Q,
1666 14