SCN5A Variant W1273C

Summary of observed carriers, functional annotations, and structural context for SCN5A W1273C. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

18%

1/11 effective observations

Estimated BrS1 penetrance

32%

3/11 effective observations

Total carriers

1

0 BrS1 · 0 LQT3 · 1 unaffected

W1273C is present in 1 alleles in gnomAD. This residue resides in a 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 1 individuals for LQT3.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density BrS (%) Penetrance Density LQT3 (%)
-12.65 1 2.38 0.853 46 4

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 11 1 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 W1273C.
Neighbour residue Distance (Å) Observed variants
1267 6
1271 9 W1271C, W1271C,
1281 12 c.3840+1G>A, V1281F,
1274 6
1258 11
1272 7
1270 6 A1270S,
1283 14 L1283M
1309 12 R1309C, R1309H,
1265 12
1279 10 V1279I,
1305 12
1273 0 W1273C, W1273C, c.3816delG,
1282 14 S1282A,
1262 13 G1262S,
1257 13
1268 8 T1268S, T1268N, T1268S,
1275 8 D1275N,
1254 11
1263 11
1253 14 E1253G,
1264 14 K1264N, K1264R, K1264N,
1312 14
1280 9
1311 14 L1311P,
1308 12 L1308F,
1250 14
1269 8 N1269S,
1276 5
1278 9 I1278N,
1266 8
1261 13
1277 5