SCN5A Variant S1710L

Summary of observed carriers, functional annotations, and structural context for SCN5A S1710L. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

1%

0/18 effective observations

Estimated BrS1 penetrance

34%

6/18 effective observations

Total carriers

8

2 BrS1 · 0 LQT3 · 6 unaffected

S1710L is present in 4 alleles 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 (%)
-5.55 1 -4.78 0.958 56 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
19026623 2009 1 0 1 0
26798387 2016 5 0 0 3 SSS
10940383 2000 1 0 1 0
30059973 2018 4 4 0 0
Literature, cohort, and gnomAD 8 6 0 2
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)
19026623 2009
26798387 2016
10940383 2000 HEK 17.7 -24.3
30059973 2018

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 S1710L.
Neighbour residue Distance (Å) Observed variants
1702 15
896 13 C896S, C896S,
1417 6
1765 12
1757 12
1715 12
1687 15
1413 11
372 11
401 13 S401P,
1756 8 I1756V,
1764 10 c.5290delG, V1764F,
371 8 Q371E,
1711 4 c.5131delG,
1754 13
1707 7
1411 15
1704 11 L1704H,
1458 12 S1458Y,
1410 15
1706 8 Q1706H, Q1706H,
1716 11 p.L1716SfsX71,
1714 11 D1714G,
376 14 R376C, R376H,
897 11 G897R, G897R, G897E,
1762 13 p.I1762del, I1762M,
1668 14 M1668T,
1753 12 T1753A,
1422 15 M1422R,
378 13
1418 9
402 12 F402L, F402L, F402L,
373 10
1768 15 I1768V
1712 7 G1712S, G1712C,
379 14
1703 12
898 11
893 15 R893C, R893H,
397 12 I397V, I397F, I397T,
405 15
1462 11
1759 9 S1759C,
1709 4 p.T1709del, T1709R, T1709M,
1420 11 G1420R, G1420D, G1420V, G1420P,
1758 12 I1758V, p.I1758del,
1755 9
393 15
1713 5
1708 7 T1708I,
1421 12
374 9 W374G,
1705 11
1717 12 L1717P,
367 14 R367C, R367H, R367L,
1763 13 V1763M, V1763L, V1763L,
1751 14
1416 10 c.4245+1G>A, c.4245+1G>C, c.4245+2T>A, A1416E, A1416G,
1465 14 p.F1465_L1480dup,
1760 6
370 12 T370M,
1752 10
1761 10 c.5280delG, L1761F, L1761H,
375 9
368 13
1710 0 S1710L,
1415 12
377 15
1419 6 K1419E,
1667 15 V1667I,
1414 9 Q1414H, Q1414H,
1664 13
1463 14 N1463Y,