SCN5A Variant c.4389_4396delCCTCTTTA

Summary of observed carriers, functional annotations, and structural context for SCN5A c.4389_4396delCCTCTTTA. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

5%

0/11 effective observations

Estimated BrS1 penetrance

42%

4/11 effective observations

Total carriers

1

1 BrS1 · 0 LQT3 · 0 unaffected

c.4389_4396delCCTCTTTA 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 3 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 (%)
NA NA NA None 50 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
28341781 2017 1 0 1 0
20129283 2010 1 0 1 0
Literature, cohort, and gnomAD 1 0 0 1
Variant features alone 15 12 0 3

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
28341781 2017

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 c.4389_4396delCCTCTTTA.
Neighbour residue Distance (Å) Observed variants
939 9 L939F,
937 11
1417 15
1765 11
839 13 L839P,
943 12 S943N,
1340 9 V1340I,
1457 9
1453 14
1455 13
1757 13
1472 12 N1472S, p.N1472del,
1339 12 p.L1339del, L1339F,
1461 5 T1461S, T1461S,
1764 14 c.5290delG, V1764F,
409 14 L409V, L409P,
1333 10
1344 11 F1344S, F1344L, F1344L, F1344L,
825 13
934 9
1458 10 S1458Y,
933 14
1471 11
935 9 L935P,
1762 12 I1762M, p.I1762del,
1470 10
1464 0 L1464P, c.4389_4396delCCTCTTTA,
1466 7 c.4396_4397insG,
944 12
1769 14
1766 14 M1766L, M1766T, M1766L, M1766V,
1768 13 I1768V,
940 12 S940N,
1334 10 I1334V,
1341 8
1468 7 V1468A, V1468F,
831 11
1462 7
938 6
942 7
1456 11
1459 11 c.4376_4379delTCTT,
1330 13 A1330D, A1330P, A1330T,
827 13
1460 6 F1460L, F1460L, F1460L,
1454 14
1338 10 L1338V,
1343 14
1345 12 W1345C, W1345C,
941 10 S941F, S941N,
1337 7
1342 14
936 11
1416 13 A1416E, c.4245+1G>C, A1416G, c.4245+2T>A, c.4245+1G>A,
1332 14 P1332Q, P1332L,
1465 5 p.F1465_L1480dup,
1760 13
1467 6
1331 14 I1331V,
1761 10 L1761H, L1761F, c.5280delG,
1469 9 I1469V,
1336 11
824 13
829 13
932 13
1335 13 M1335R,
832 11
835 13 S835L, S835A,
828 9 L828V,
931 13
1463 5 N1463Y,