SCN5A Variant L1717P

Summary of observed carriers, functional annotations, and structural context for SCN5A L1717P. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

1%

0/11 effective observations

Estimated BrS1 penetrance

53%

5/11 effective observations

Total carriers

1

1 BrS1 · 0 LQT3 · 0 unaffected

L1717P 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 (%)
-6.48 1 -6.27 0.992 67 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
22840528 2012 1 0 1 0
24721456 2014 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)
22840528 2012
24721456 2014

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 L1717P.
Neighbour residue Distance (Å) Observed variants
1746 11 A1746T, A1746V,
1417 12
1406 14 G1406R, G1406R, G1406E,
1715 6
1687 10
1745 10
1756 11 I1756V
1675 13
1743 11 G1743R, G1743R, G1743E,
1711 11 c.5131delG,
1723 12 T1723N,
1754 13
1707 10
1398 14 V1398M,
1694 12
1411 11
1407 12
1704 13 L1704H,
1410 9
1706 12 Q1706H, Q1706H,
1747 10 V1747M,
1716 5 p.L1716SfsX71,
1714 5 D1714G,
1688 11
1684 15 W1684R, W1684R,
1671 14
1423 14 D1423H,
1692 14
1744 9 S1744I,
1721 6
1753 10 T1753A,
1693 14
1712 8 G1712S, G1712C,
1680 15 A1680T, A1680P,
1703 12
1412 14 L1412F,
1719 6
1408 14 G1408R, G1408R,
1709 15 p.T1709del, T1709R, T1709M,
1420 11 G1420R, G1420D, G1420V, G1420P,
1678 14 N1678S,
1755 12
1401 13
1399 9
1713 7
1424 14 I1424V,
1748 7 p.G1748del, G1748D,
1708 14 T1708I,
1683 13
1409 14 Y1409C, Y1409X,
1400 10 V1400I,
1718 5 S1718R, S1718R, S1718R,
1700 15
1717 0 L1717P,
1751 9
1416 15 c.4245+1G>A, c.4245+1G>C, c.4245+2T>A, A1416E, A1416G,
1682 12
1750 11 L1750F,
1752 6
1722 10 N1722D,
1686 9
1749 8 I1749N,
375 13
1710 12 S1710L,
1720 5 c.5157delC,
1415 14
1679 11
1685 10
1419 11 K1419E,
1414 9 Q1414H, Q1414H,
1413 11