SCN5A Variant R1306S

Summary of observed carriers, functional annotations, and structural context for SCN5A R1306S. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

3%

0/11 effective observations

Estimated BrS1 penetrance

18%

1/11 effective observations

Total carriers

1

0 BrS1 · 0 LQT3 · 1 unaffected

R1306S 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 (%)
-5.29 1 -4.64 0.829 21 3

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 R1306S.
Neighbour residue Distance (Å) Observed variants
1271 15 W1271C,
1245 11 M1245I,
1218 7 S1218I, S1218T,
1281 8 c.3840+1G>A, V1281F,
1304 7 T1304M,
1217 11
1243 7 D1243N,
1274 10
1216 11 L1216V,
1285 10
1299 13 c.3894delC,
1220 11 G1220E,
1673 11
1213 14
1272 15
1252 14
1283 11 L1283M,
1241 13
1309 7 R1309C, R1309H,
1226 15
1669 12
1221 10 A1221V,
1242 9
1219 8 S1219N,
1672 15 S1672Y,
1251 12 V1251M,
1313 15
1279 9 V1279I,
1239 11 L1239P,
1310 10
1306 0 R1306S, R1306H,
1244 12 K1244E,
1286 13
1305 6
1246 7
1282 7 S1282A,
1302 9 p.L1302Vfs18,
1247 8 T1247I,
1307 7
1223 12 c.3667delG,
1275 9 D1275N,
1222 8 L1222R, p.L1222LfsX7,
1300 14
1674 13 F1674V,
1254 13
1215 8 I1215V,
1301 10
1214 10 M1214T,
1212 13 p.I1212del,
1253 12 E1253G,
1284 12
1211 12
1280 11
1311 13 L1311P,
1677 14
1308 8 L1308F,
1250 7
1224 15
1670 12
1240 12 E1240Q,
1248 12
1225 12 E1225K, G1225K,
1276 13
1278 6 I1278N,
1238 15
1249 10 V1249D,
1277 11
1303 6 R1303Q, R1303W,
1666 15