SCN5A Variant V1543A

Summary of observed carriers, functional annotations, and structural context for SCN5A V1543A. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

5%

0/12 effective observations

Estimated BrS1 penetrance

8%

0/12 effective observations

Total carriers

2

0 BrS1 · 0 LQT3 · 2 unaffected

V1543A is present in 2 alleles in gnomAD. This residue resides in a Non_Hotspot region for Brugada syndrome and a Mild_Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 0 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 (%)
-3.6 0.303 -1.79 0.87 2 10

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
Literature, cohort, and gnomAD 2 2 0 0
Variant features alone 15 15 0 0

Totals may differ from individual publications due to duplicate patients removed during curation.

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 V1543A.
Neighbour residue Distance (Å) Observed variants
266 9 L266H,
1544 4 T1544P,
270 12 Q270K,
1627 11
1567 10 F1567L, F1567L, F1567L,
1536 10
1549 13
1538 9
1566 14
1556 13
1543 0 V1543L, V1543L, V1543A,
1534 14
1542 5
361 15
1571 14 F1571C,
1564 11
258 14 V258A,
1546 5 M1546T,
1545 7
1630 11 I1630V, I1630R
1626 11 R1626C, R1626H, R1626P, R1626L,
267 13
1560 10 L1560F, L1560F,
262 10 S262G,
357 13
362 14
261 15
1559 13 I1559V,
1628 15
1539 7 C1539Y, C1539F,
269 12
1535 13
1537 10
259 12
1633 14
1548 10 E1548K, G1548K,
265 12 A265V,
358 10
263 11 V263I,
359 14 A359T, p.A359PfsX12,
1629 14 R1629G, R1629X, R1629Q,
1547 7 V1547L, V1547L,
1563 10
1541 6
1540 5
268 15 G268S,
1561 14
1623 14 c.4867delC, R1623X, R1623Q, R1623L,