SCN5A Variant I1768V

Summary of observed carriers, functional annotations, and structural context for SCN5A I1768V. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

68%

24/41 effective observations

Estimated BrS1 penetrance

2%

0/41 effective observations

Total carriers

31

0 BrS1 · 22 LQT3 · 9 unaffected

I1768V has not been reported in gnomAD. This residue resides in a Non_Hotspot region for Brugada syndrome and a Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 0 individuals for Brugada syndrome and 2 individuals for LQT3.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density BrS (%) Penetrance Density LQT3 (%)
-0.93 1 5.57 0.9 7 64

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
12650885 2003 1 1 0 0
12566525 2003 1 1 0 0
17905336 2007 1 1 0 0
22677073 2012 1 0 0 1 SUDS
23683917 2013 1 0 0 1 SUD
25804018 2014 2 2 0 0
26669661 2016 27 18 0 0
25904541 2015 3 3 0 0
27566755 2016 58 58 0 0
12209021 2002 1 1 0 0
30059973 2018 9 9 0 0
Literature, cohort, and gnomAD – 31 9 22 0 –
Variant features alone – 15 13 2 0 – –

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)
12695286 2003 HEK 100 100
12650885 2003 Xeno 102 0.7 0.9 94
30059973 2018
12566525 2003
16829642 2006
17905336 2007
22677073 2012
23683917 2013
25804018 2014
26669661 2016
29017927 2017
17556201 2007
25904541 2015
27566755 2016
17556202 2007
12209021 2002 HEK 0 7.6 20

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 I1768V.
Neighbour residue Distance (Å) Observed variants
403 9
414 15 M414V,
939 12 L939F,
1659 14
404 11 L404Q, L404V,
1773 9
1765 5
1653 11
1472 12 p.N1472del, N1472S,
1771 6 I1771T,
401 10 S401P,
1652 15 M1652R, M1652T,
1764 7 V1764F, c.5290delG,
371 13 Q371E,
409 8 L409V, L409P,
928 13 L928P,
1650 12 L1650F,
1656 12
934 15
1477 14 K1477N, K1477N,
933 15
1471 12
935 10 L935P,
412 13 V412D,
1762 10 p.I1762del, I1762M,
1470 7
1464 13 c.4389_4396delCCTCTTTA, L1464P,
927 14 N927K, N927S, N927K,
1466 6 c.4396_4397insG,
1776 13
369 14 M369K,
1767 6 Y1767C,
1660 10 I1660S, I1660V,
1654 14
1769 4
402 8 F402L, F402L, F402L,
1766 7 M1766V, M1766L, M1766L, M1766T,
1649 14 A1649V,
1768 0 I1768V,
1774 11 N1774D, c.5321_5324dupACTT,
1473 9 F1473C, F1473S,
1468 11 V1468F, V1468A,
1663 14
399 14
397 14 I397F, I397T, I397V,
405 8
1657 10
1462 13
1474 13
1759 12 S1759C,
938 14
1327 14
1709 13 p.T1709del, T1709R, T1709M,
1758 15 p.I1758del, I1758V,
1330 15 A1330D, A1330P, A1330T,
1772 6 L1772V,
1323 13 V1323G,
410 9 A410V,
1770 7 I1770V,
1658 14
1708 14 T1708I,
413 12 A413T, A413E,
408 11
1322 15 c.3963+2T>C, c.3963+4A>G,
407 10
1326 13 A1326S,
936 12
1763 9 V1763L, V1763L, V1763M,
1465 12 p.F1465_L1480dup,
1760 11
1467 10
1775 12 p.F1775LfsX15, F1775V,
370 15 T370M,
1661 13 G1661R, G1661R, G1661E,
1761 11 L1761H, c.5280delG, L1761F,
1655 15
1469 8 I1469V,
406 5 N406K, N406S, N406K,
1710 15 S1710L,
411 13 V411M,
932 10
398 12
400 12 G400A, G400E, G400R, G400R,
931 14
1664 13
1463 11 N1463Y,