SCN5A Variant G1220E

Summary of observed carriers, functional annotations, and structural context for SCN5A G1220E. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

12%

0/11 effective observations

Estimated BrS1 penetrance

21%

2/11 effective observations

Total carriers

1

0 BrS1 · 0 LQT3 · 1 unaffected

G1220E is present in 1 alleles in gnomAD. This residue resides in a Mild_Hotspot region for Brugada syndrome and a Mild_Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 2 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 (%)
-7.77 0.999 -4.8 0.899 21 14

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 13 0 2

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 G1220E.
Neighbour residue Distance (Å) Observed variants
1245 14 M1245I, M1245I, M1245I,
1218 5 S1218T, S1218I,
1304 12 T1304M,
1217 6
1243 13 D1243N,
1216 7 L1216V,
1234 15
1698 13 A1698T,
1220 0 G1220E,
1673 10
1213 11
1241 14
1309 13 R1309C, R1309H,
1226 12
1669 8
1221 3 A1221V,
1242 11
1668 14 M1668T,
1676 13 M1676T, M1676I, M1676I, M1676I,
1219 4 S1219N,
1672 12 S1672Y,
1239 10 L1239P,
1310 11
1306 11 R1306S, R1306H,
1665 12
1305 15
1246 12
1235 11
1701 13 M1701I, M1701I, M1701I
1307 10
1228 14 Y1228H, Y1228C, Y1228F,
1223 5 c.3667delG,
1697 10
1222 5 p.L1222LfsX7, L1222R,
1229 14
1215 9 I1215V,
1301 15
1214 11 M1214T,
1212 13 p.I1212del,
1696 13
1700 14
1308 14 L1308F,
1224 6
1670 12
1240 14 E1240Q,
1225 10 E1225K, G1225K,
1238 12
1303 12 R1303W, R1303Q,
1666 12