SCN5A Variant C1575S

Summary of observed carriers, functional annotations, and structural context for SCN5A C1575S. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

6%

0/11 effective observations

Estimated BrS1 penetrance

28%

3/11 effective observations

Total carriers

1

0 BrS1 · 0 LQT3 · 1 unaffected

C1575S is present in 1 alleles 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 3 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 (%)
-7.55 0.485 0.49 0.916 41 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
Literature, cohort, and gnomAD – 1 1 0 0 –
Variant features alone – 15 12 0 3 – –

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 C1575S.
Neighbour residue Distance (Å) Observed variants
1569 10 A1569P,
1525 10 V1525M, V1525A,
1524 12 I1524T,
1586 7
1518 14
1567 14 F1567L, F1567L, F1567L,
1538 13
1531 12
1566 15
1568 10
1587 11 F1587V,
1602 11
1534 10
1601 13 L1601H,
1522 14
1575 0 C1575S, C1575S
1600 9
1571 7 F1571C,
1521 11 I1521K, I1521T,
1572 5
1570 10 p.I1570dup, I1570V, p.1570_F1571insI,
1599 7
1526 14 T1526P,
1583 12 R1583H, R1583C,
1580 9
1626 14 R1626H, R1626C, R1626P, R1626L,
1603 12 I1603F,
1625 14
1585 15 Y1585C,
1576 5
1596 7 F1596C, F1596I,
1589 12
1584 14
1632 12 R1632L, R1632C, R1632H,
1597 10 V1597M,
1530 10
1573 5
1535 13
1537 13
1594 12 F1594S,
1588 14 T1588I,
1581 10 A1581S,
1591 13 W1591X,
1593 10 I1593M,
1595 7
1629 11 R1629Q, R1629G, R1629X,
1574 4 c.4719C>T, E1574K,
1533 14 T1533I,
1592 8
1578 5 c.4732_4733dupAA,
1590 14
1582 10 L1582P,
1579 6 L1579fsX53,
1598 10 V1598A,
1577 6