SCN5A Variant I1559V

Summary of observed carriers, functional annotations, and structural context for SCN5A I1559V. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

3%

0/18 effective observations

Estimated BrS1 penetrance

3%

0/18 effective observations

Total carriers

8

0 BrS1 · 0 LQT3 · 8 unaffected

I1559V is present in 8 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 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 (%)
-0.48 0.026 3.26 0.573 3 8

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 – 8 8 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 I1559V.
Neighbour residue Distance (Å) Observed variants
1560 4 L1560F, L1560F,
1564 9
1559 0 I1559V,
1544 9 T1544P,
1553 10 S1553R, S1553R, S1553R,
1547 10 V1547L, V1547L,
1563 6
1541 13
1554 9
1567 11 F1567L, F1567L, F1567L
1546 15 M1546T,
1540 13
1549 13
1552 12 Q1552R, Q1552L,
1566 11
1556 6
1568 14
1545 13
1565 10 L1565M,
1543 13 V1543L, V1543L, V1543A,
1558 5
1548 11 E1548K, G1548K,
1561 6
1557 7 I1557V,
1555 8 E1555K,
1562 5