SCN5A Variant C1539F

Summary of observed carriers, functional annotations, and structural context for SCN5A C1539F. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

12%

0/11 effective observations

Estimated BrS1 penetrance

9%

1/11 effective observations

Total carriers

1

0 BrS1 · 0 LQT3 · 1 unaffected

C1539F is present in 1 alleles in gnomAD. This residue resides in a Non_Hotspot region for Brugada syndrome and a Non_Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 1 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 (%)
-9.39 0.998 1.22 0.84 1 1

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 1 1 0 0
Variant features alone 15 14 0 1

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 C1539F.
Neighbour residue Distance (Å) Observed variants
266 12 L266H,
1544 10 T1544P,
1627 10
1567 10 F1567L, F1567L, F1567L,
1536 6
1538 4
1531 13
1566 14
1635 13
1568 15
1634 13 L1634P
1543 7 V1543L, V1543L, V1543A,
1534 9
1542 6
260 14
1571 11 F1571C,
1564 14
1570 13 p.1570_F1571insI, I1570V, p.I1570dup,
258 13 V258A,
1529 15
1546 10 M1546T,
1545 10
1630 7 I1630V, I1630R,
1532 10 V1532I, V1532F,
1626 11 R1626C, R1626H, R1626P, R1626L,
267 15
1625 15
262 11 S262G,
256 15
1628 11
1632 9 R1632C, R1632H, R1632L,
1539 0 C1539Y, C1539F,
1530 14
255 14
1535 6
1537 6
259 10
1633 8
1591 14 W1591X,
1595 13
265 15 A265V,
1637 14
1636 11
358 14
263 11 V263I,
1629 9 R1629G, R1629X, R1629Q,
1547 14 V1547L, V1547L,
1574 14 c.4719C>T, E1574K,
1533 10 T1533I,
1563 13
1541 7
1540 5
1631 10 G1631D,
1598 15 V1598A,