SCN5A Variant L1311P

Summary of observed carriers, functional annotations, and structural context for SCN5A L1311P. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

1%

0/11 effective observations

Estimated BrS1 penetrance

52%

5/11 effective observations

Total carriers

1

1 BrS1 · 0 LQT3 · 0 unaffected

L1311P has not been reported 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 4 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 (%)
-6.19 1 -5.43 0.96 68 1

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
26941339 2016 1 0 1 0
20129283 2010 1 0 1 0
Literature, cohort, and gnomAD – 1 0 0 1 –
Variant features alone – 15 11 0 4 – –

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)
26941339 2016
20129283 2010

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 L1311P.
Neighbour residue Distance (Å) Observed variants
1328 12 V1328M,
1659 13
1271 7 W1271C, W1271C,
1218 14 S1218T, S1218I,
1304 13 T1304M,
1315 7
1274 9
1216 11 L1216V,
1314 6 c.3940_3941delCT,
1320 10 M1320I, M1320I, M1320I,
1673 14
1666 7
1272 12
1270 11 A1270S,
1309 8 R1309C, R1309H,
1669 10
1671 12
1668 13 M1668T,
1219 12 S1219N,
1672 15 S1672Y,
1313 7
1660 13 I1660V, I1660S,
1310 4
1316 11 R1316Q, R1316L,
1306 13 R1306S, R1306H,
1319 14 G1319V,
1665 12
1305 11
1273 14 c.3816delG, W1273C, W1273C,
1663 9
1662 11
1324 9
1317 12 F1317C,
1327 11
1307 8
1758 13 I1758V, p.I1758del,
1275 11 D1275N,
1321 13 R1321K,
1674 14 F1674V,
1323 12 V1323G,
1215 10 I1215V,
1212 11 p.I1212del,
1322 15 c.3963+2T>C, c.3963+4A>G,
1211 14
1312 7
1326 14 A1326S,
1763 14 V1763M, V1763L, V1763L
1311 0 L1311P,
1308 6 L1308F,
1670 8
1661 13 G1661R, G1661R, G1661E,
1331 15 I1331V,
1269 13 N1269S,
1325 13 N1325S,
1278 12 I1278N,
1277 14
1667 9 V1667I,
1664 12