SCN5A Variant L1601H

Summary of observed carriers, functional annotations, and structural context for SCN5A L1601H. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

3%

0/12 effective observations

Estimated BrS1 penetrance

14%

1/12 effective observations

Total carriers

2

0 BrS1 · 0 LQT3 · 2 unaffected

L1601H is present in 2 alleles in gnomAD. This residue resides in a Mild_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 (%)
-6.41 1 -4.03 0.971 12 2

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 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 L1601H.
Neighbour residue Distance (Å) Observed variants
1569 14 A1569P,
1627 13
1624 11 V1624I,
1568 11
1602 5
1601 0 L1601H,
1609 12 S1609W, S1609L,
1575 13 C1575S, C1575S,
1608 10
1613 13 Q1613L, Q1613H, Q1613H,
1600 5
1571 12 F1571C,
1615 14 Y1615X,
1572 12
1564 13
1599 6
1626 9 R1626C, R1626H, R1626P, R1626L,
1603 6 I1603F,
1625 8
1606 9 T1606I,
1610 12 D1610G,
1596 9 F1596I, F1596C,
1628 13
1597 6 V1597M,
1620 11 T1620K, T1620M,
1565 14 L1565M,
1594 12 F1594S,
1614 14
1593 13 I1593M,
1595 11
1619 10 P1619Q, P1619L, c.4856delC,
1629 12 R1629G, R1629X, R1629Q
1605 7 c.4813+2_4813+5dupTGGG, c.4813+3_4813+6dupGGGT, c.4813+5insTGGG, G1605C, G1605D,
1611 15 I1611V,
1574 15 c.4719C>T, E1574K,
1541 15
1616 9
1607 11
1592 15
1617 5 p.F1617del,
1604 5 c.4810+3_4810+6dupGGGT, V1604M,
1622 6
1618 8
1621 9
1598 6 V1598A,
1623 11 c.4867delC, R1623X, R1623Q, R1623L,