SCN5A Variant T1709R

Summary of observed carriers, functional annotations, and structural context for SCN5A T1709R. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

0%

0/11 effective observations

Estimated BrS1 penetrance

55%

6/11 effective observations

Total carriers

1

1 BrS1 · 0 LQT3 · 0 unaffected

T1709R 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 5 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 -5.01 0.979 73 0

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 10 0 5

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 T1709R.
Neighbour residue Distance (Å) Observed variants
403 15
1702 12
896 15 C896S, C896S,
1417 10
1765 11
396 12 V396A, V396L,
1757 13
1715 14
372 11
401 10 S401P,
1756 10 I1756V,
1764 8 c.5290delG, V1764F,
371 6 Q371E,
1711 5 c.5131delG,
1754 15
1707 7
1704 9 L1704H,
1706 7 Q1706H, Q1706H,
1716 12 p.L1716SfsX71,
1714 14 D1714G,
376 14 R376H, R376C,
1671 15
897 13 G897R, G897E, G897R,
1762 13 I1762M, p.I1762del,
1668 11 M1668T,
1692 15
369 12 M369K,
1753 15 T1753A,
1767 12 Y1767C,
1660 14 I1660S, I1660V,
378 11
1418 12
402 9 F402L, F402L, F402L,
1766 14 M1766V, M1766T, M1766L, M1766L,
1665 15
373 10
1768 13 I1768V,
1712 9 G1712S, G1712C,
379 13
1703 11
898 13
1663 15
399 14
397 8 I397F, I397V, I397T,
405 13
1462 14
1759 8 S1759C,
1709 0 T1709R, T1709M, p.T1709del,
1701 13 M1701I, M1701I, M1701I,
1420 15 G1420V, G1420R, G1420P, G1420D,
1758 13 I1758V, p.I1758del,
1755 10
395 15
393 11
1713 8
390 14
394 11
1708 4 T1708I,
374 7 W374G,
1705 8
1700 15
1717 15 L1717P,
367 13 R367L, R367C, R367H,
1763 11 V1763L, V1763M, V1763L,
1416 14 A1416E, c.4245+2T>A, c.4245+1G>C, c.4245+1G>A, A1416G,
1760 7
370 11 T370M,
1752 12
1661 13 G1661R, G1661R, G1661E,
1761 11 L1761F, L1761H, c.5280delG,
375 10
406 14 N406K, N406K, N406S,
368 10
1710 4 S1710L,
377 13
398 11
400 13 G400A, G400R, G400E, G400R,
1419 10 K1419E,
1667 13 V1667I,
1414 14 Q1414H, Q1414H,
1664 10