SCN5A Variant T1544P

Summary of observed carriers, functional annotations, and structural context for SCN5A T1544P. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

48%

2/11 effective observations

Estimated BrS1 penetrance

11%

1/11 effective observations

Total carriers

1

0 BrS1 · 1 LQT3 · 0 unaffected

T1544P 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 1 individuals for Brugada syndrome and 1 individuals for LQT3.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density BrS (%) Penetrance Density LQT3 (%)
-5.48 0.996 -3.81 0.959 4 52

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
23631430 2013 1 1 0 0
Literature, cohort, and gnomAD 1 0 1 0
Variant features alone 15 13 1 1

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)
23631430 2013

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 T1544P.
Neighbour residue Distance (Å) Observed variants
266 10 L266H,
1544 0 T1544P,
270 10 Q270K,
1627 11
1567 8 F1567L, F1567L, F1567L,
1624 15 V1624I,
1536 12
1552 14 Q1552R, Q1552L,
1549 12
1538 10
1566 11
1556 10
1568 13
1543 4 V1543L, V1543L, V1543A,
1558 13
1534 15
1542 7
1557 12 I1557V,
1562 12
1571 13 F1571C,
1564 7
1570 14 p.1570_F1571insI, I1570V, p.I1570dup,
1546 7 M1546T,
1545 5
1630 13 I1630V, I1630R
1626 10 R1626C, R1626H, R1626P, R1626L,
267 14
1560 6 L1560F, L1560F,
262 13 S262G,
357 14
273 14
1559 9 I1559V,
1628 15
1553 14 S1553R, S1553R, S1553R,
1539 10 C1539Y, C1539F,
269 11
1535 15
1537 10
1565 12 L1565M,
1548 7 E1548K, G1548K,
1555 15 E1555K,
265 14 A265V,
358 11
263 13 V263I,
1629 14 R1629G, R1629X, R1629Q,
1547 6 V1547L, V1547L,
1563 6
1541 5
1540 7
268 15 G268S,
1622 14
1561 10
1623 12 c.4867delC, R1623X, R1623Q, R1623L,