SCN5A Variant T1620K

Summary of observed carriers, functional annotations, and structural context for SCN5A T1620K. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

63%

5/13 effective observations

Estimated BrS1 penetrance

17%

2/13 effective observations

Total carriers

3

0 BrS1 · 3 LQT3 · 0 unaffected

T1620K has not been reported in gnomAD. This residue resides in a Mild_Hotspot region for Brugada syndrome and a Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 2 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 (%)
-5.35 0.978 -1.94 0.938 28 53

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
18065446 2008 4 3 0 1 CCD
Literature, cohort, and gnomAD – 3 0 3 0 –
Variant features alone – 15 11 2 2 – –

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)
21552533 2011 HEK 94 -4.5 -10.9 155
18065446 2008 HEK -5 9.5

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 T1620K.
Neighbour residue Distance (Å) Observed variants
271 6 L271V,
266 12 L266H,
270 8 Q270K,
1627 11
385 12 A385T,
1624 7 V1624I,
355 14 F355I, F355C,
391 12
388 11 I388S,
1602 14
1601 11 L1601H,
1613 12 Q1613L, Q1613H, Q1613H,
1615 15 Y1615X,
384 15 S384T,
329 14
386 13 G386R, G386R, G386E,
1545 12
1626 11 R1626C, R1626H, R1626P, R1626L
267 10
1625 9
1610 15 D1610G,
272 10
274 14 G274C,
273 12
1628 13
1597 14 V1597M,
392 12
389 10 Y389H, Y389X,
269 12
1620 0 T1620K, T1620M,
395 15
275 12 N275K, N275K,
264 14
1614 11
1548 14 E1548K, G1548K,
265 15 A265V,
1619 4 P1619Q, P1619L, c.4856delC,
1605 13 c.4813+2_4813+5dupTGGG, c.4813+3_4813+6dupGGGT, c.4813+5insTGGG, G1605C, G1605D,
1616 13
1617 8 p.F1617del,
268 11 G268S,
1604 14 c.4810+3_4810+6dupGGGT, V1604M,
1622 7
1618 5
1621 4
1598 13 V1598A,
1623 5 c.4867delC, R1623X, R1623Q, R1623L,