SCN5A Variant V1323G

Summary of observed carriers, functional annotations, and structural context for SCN5A V1323G. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

14%

0/11 effective observations

Estimated BrS1 penetrance

53%

5/11 effective observations

Total carriers

1

1 BrS1 · 0 LQT3 · 0 unaffected

V1323G has not been reported in gnomAD. This residue resides in a Hotspot region for Brugada syndrome and a Mild_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 (%)
-6.76 0.993 -6.21 0.97 69 23

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
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)
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 V1323G.
Neighbour residue Distance (Å) Observed variants
1328 9 V1328M,
1659 7
1271 14 W1271C, W1271C,
1480 11 c.4437+5G>A, c.4438-1C>T,
1773 13
1765 12
1653 12
1472 11 p.N1472del, N1472S,
1315 8
1771 13 I1771T,
1314 9 c.3940_3941delCT,
1320 4 M1320I, M1320I, M1320I,
1764 12 c.5290delG, V1764F,
1666 13
1656 8
1477 10 K1477N, K1477N,
1471 15
1762 11 p.I1762del, I1762M,
1470 13
1466 15 c.4396_4397insG,
1767 10 Y1767C,
1313 13
1660 6 I1660V, I1660S,
1654 14
1329 10 G1329S,
1310 15
1769 10
1316 13 R1316Q, R1316L,
1766 7 M1766L, M1766V, M1766L, M1766T,
1319 6 G1319V,
1665 15
1768 13 I1768V,
1774 14 N1774D, c.5321_5324dupACTT
1479 12
1473 7 F1473S, F1473C,
1334 15 I1334V,
1468 14 V1468F, V1468A,
1663 8
1657 10
1474 13
1759 13 S1759C,
1662 10
1324 4
1317 10 F1317C,
1327 7
1758 13 I1758V, p.I1758del,
1318 10
1330 11 A1330T, A1330P, A1330D,
1772 15 L1772V,
1321 9 R1321K,
1323 0 V1323G,
1770 9 I1770V,
1322 4 c.3963+2T>C, c.3963+4A>G,
1312 12
1326 6 A1326S,
1763 9 V1763M, V1763L, V1763L,
1311 12 L1311P,
1476 8 Q1476X, Q1476R,
1661 10 G1661R, G1661R, G1661E,
1331 13 I1331V,
1655 11
1475 13 p.Q1475NfsX6, Q1475L,
1469 11 I1469V,
1325 6 N1325S,
1667 13 V1667I,
1664 11
1658 12