SCN5A Variant R1303W

Summary of observed carriers, functional annotations, and structural context for SCN5A R1303W. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

9%

0/11 effective observations

Estimated BrS1 penetrance

10%

1/11 effective observations

Total carriers

1

0 BrS1 · 0 LQT3 · 1 unaffected

R1303W is present in 1 alleles in gnomAD. This residue resides in a Non_Hotspot region for Brugada syndrome and a Mild_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 (%)
-7.08 1 -5.91 0.816 4 11

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 R1303W.
Neighbour residue Distance (Å) Observed variants
1245 12 M1245I, M1245I, M1245I,
1218 9 S1218T, S1218I,
1297 15
1281 8 c.3840+1G>A, V1281F,
1304 6 T1304M,
1217 14
1243 6 D1243N,
1274 15
1216 15 L1216V,
1285 8
1299 9 c.3894delC,
1220 12 G1220E,
1673 10
1675 14
1298 13 P1298L,
1283 12 L1283M,
1241 12
1309 13 R1309C, R1309H,
1226 11
1288 12 A1288G,
1669 14
1221 10 A1221V,
1242 8
1676 13 M1676T, M1676I, M1676I, M1676I,
1219 10 S1219N,
1672 14 S1672Y,
1279 12 V1279I,
1239 8 L1239P,
1310 14
1306 6 R1306S, R1306H,
1244 11 K1244E,
1286 12
1305 8
1282 8 S1282A,
1246 10
1235 13
1302 6 p.L1302Vfs18,
1247 10 T1247I,
1237 13 V1237F,
1307 10
1289 13
1678 14 N1678S
1223 11 c.3667delG,
1275 14 D1275N,
1222 7 p.L1222LfsX7, L1222R,
1300 10
1674 12 F1674V,
1229 12
1215 13 I1215V,
1301 6
1214 15 M1214T,
1284 10
1280 13
1677 11
1308 12 L1308F,
1250 11
1224 13
1670 13
1240 8 E1240Q,
1248 14
1225 8 E1225K, G1225K,
1287 14
1278 10 I1278N,
1238 13
1236 12 K1236R, K1236N, K1236N,
1249 14 V1249D,
1277 14
1303 0 R1303W, R1303Q,