SCN5A Variant L1222R

Summary of observed carriers, functional annotations, and structural context for SCN5A L1222R. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

47%

2/11 effective observations

Estimated BrS1 penetrance

15%

1/11 effective observations

Total carriers

1

0 BrS1 · 1 LQT3 · 0 unaffected

L1222R has not been reported in gnomAD. This residue resides in a Mild_Hotspot region for Brugada syndrome and a Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 1 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 (%)
-5.82 0.926 -5.27 0.946 14 51

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
30059973 2018 1 1 0 0
Literature, cohort, and gnomAD 1 0 1 0
Variant features alone 15 13 1 1

Totals may differ from individual publications due to duplicate patients removed during curation.

Functional data

Peak and late/persistent current values are relative to wild-type (100% indicates no change). V1/2 activation and inactivation denote the membrane potentials (mV) at which half-maximal current is achieved.

Published electrophysiology measurements.
PubMed ID Year Cell Type Peak Current (% WT) V1/2 Activation (mV) V1/2 Inactivation (mV) Late/Persistent Current (% WT)
30059973 2018

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 L1222R.
Neighbour residue Distance (Å) Observed variants
1245 13 M1245I,
1218 6 S1218I, S1218T,
1281 14 c.3840+1G>A, V1281F,
1304 8 T1304M,
1217 9
1243 10 D1243N,
1216 10 L1216V,
1234 14
1698 14 A1698T,
1285 15
1299 15 c.3894delC,
1220 5 G1220E,
1673 7
1675 12
1213 14
1241 13
1309 13 R1309H, R1309C,
1226 8
1669 9
1671 14
1221 4 A1221V,
1242 9
1668 15 M1668T,
1676 10 M1676T, M1676I,
1219 5 S1219N,
1672 10 S1672Y
1239 7 L1239P,
1310 12
1306 8 R1306H, R1306S,
1665 14
1305 11
1246 11
1235 10
1282 14 S1282A,
1302 12 p.L1302Vfs18,
1247 14 T1247I,
1237 14 V1237F,
1701 14 M1701I,
1307 8
1228 13 Y1228C, Y1228H, Y1228F,
1678 14 N1678S,
1223 5 c.3667delG,
1697 10
1222 0 L1222R, p.L1222LfsX7,
1227 13
1300 15
1674 12 F1674V,
1229 11
1215 10 I1215V,
1301 10
1214 13 M1214T,
1696 12
1700 14
1677 11
1308 12 L1308F,
1250 14
1224 7
1670 11
1240 11 E1240Q,
1225 6 E1225K, G1225K,
1278 13 I1278N,
1238 11
1236 13 K1236R, K1236N,
1303 7 R1303W, R1303Q,
1666 13