SCN5A Variant P1619L

Summary of observed carriers, functional annotations, and structural context for SCN5A P1619L. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

18%

1/11 effective observations

Estimated BrS1 penetrance

23%

2/11 effective observations

Total carriers

1

0 BrS1 · 0 LQT3 · 1 unaffected

P1619L is present in 1 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 2 individuals for Brugada syndrome and 1 individuals for LQT3.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density BrS (%) Penetrance Density LQT3 (%)
-9.25 0.977 -0.86 0.905 31 16

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 1 2 – –

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 P1619L.
Neighbour residue Distance (Å) Observed variants
271 9 L271V,
266 14 L266H,
270 9 Q270K,
1627 12
385 15 A385T,
1624 9 V1624I,
388 15 I388S,
1602 11
1601 10 L1601H,
1609 13 S1609W, S1609L,
1557 14 I1557V,
1608 14
1613 9 Q1613L, Q1613H, Q1613H,
1600 14
1615 13 Y1615X,
1612 13
1564 13
1599 15
1545 12
1626 10 R1626C, R1626H, R1626P, R1626L
267 12
1603 14 I1603F,
1625 10
1606 12 T1606I,
1560 15 L1560F, L1560F,
1610 11 D1610G,
272 13
274 15 G274C,
273 12
1628 15
1597 14 V1597M,
389 13 Y389H, Y389X,
269 13
1620 4 T1620K, T1620M,
275 13 N275K, N275K,
1614 10
1548 13 E1548K, G1548K,
1619 0 P1619Q, P1619L, c.4856delC,
1605 10 c.4813+2_4813+5dupTGGG, c.4813+3_4813+6dupGGGT, c.4813+5insTGGG, G1605C, G1605D,
1611 15 I1611V,
1541 15
1616 11
1617 6 p.F1617del,
268 13 G268S,
1604 11 c.4810+3_4810+6dupGGGT, V1604M,
1622 6
1618 4
1621 7
1598 12 V1598A,
1561 14
1623 5 c.4867delC, R1623X, R1623Q, R1623L,