SCN5A Variant F1622L

Summary of observed carriers, functional annotations, and structural context for SCN5A F1622L. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

34%

1/10 effective observations

Estimated BrS1 penetrance

22%

2/10 effective observations

Total carriers

0

0 BrS1 · 0 LQT3 · 0 unaffected

F1622L has not been reported in gnomAD. This residue resides in a Mild_Hotspot region for Brugada syndrome and a 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 (%)
NA NA NA 0.827 26 44

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 – 0 0 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 F1622L.
Neighbour residue Distance (Å) Observed variants
271 12 L271V,
266 13 L266H
1569 14 A1569P,
1544 14 T1544P,
270 11 Q270K,
1627 9
1567 13 F1567L, F1567L, F1567L,
1624 7 V1624I,
1538 13
1568 10
1602 7
1542 13
1601 6 L1601H,
1609 14 S1609W, S1609L,
1608 13
1613 12 Q1613L, Q1613H, Q1613H,
1600 10
1571 12 F1571C,
1572 14
1564 10
1599 9
1545 10
1630 15 I1630V, I1630R,
1626 5 R1626C, R1626H, R1626L, R1626P,
267 12
1603 10 I1603F,
1625 6
1606 10 T1606I,
1560 14 L1560F, L1560F,
1610 13 D1610G,
1596 13 F1596I, F1596C,
1628 11
1597 9 V1597M,
269 15
1620 7 T1620K, T1620M,
1565 12 L1565M,
1594 12 F1594S,
1614 14
1548 14 E1548K, G1548K,
1593 15 I1593M,
1595 12
1619 6 c.4856delC, P1619L, P1619Q,
1629 11 R1629X, R1629Q, R1629G,
1605 8 G1605C, G1605D, c.4813+2_4813+5dupTGGG, c.4813+5insTGGG, c.4813+3_4813+6dupGGGT,
1563 14
1541 11
1616 12
1607 13
1617 6 p.F1617del,
268 15 G268S,
1604 9 V1604M, c.4810+3_4810+6dupGGGT,
1622 0
1618 7
1621 7
1598 6 V1598A,
1561 13
1623 6 c.4867delC, R1623Q, R1623X, R1623L,