SCN5A Variant R1626L

Summary of observed carriers, functional annotations, and structural context for SCN5A R1626L. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

31%

1/11 effective observations

Estimated BrS1 penetrance

11%

1/11 effective observations

Total carriers

1

0 BrS1 · 0 LQT3 · 1 unaffected

R1626L is present in 1 alleles in gnomAD. This residue resides in a Non_Hotspot region for Brugada syndrome and a Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 1 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 (%)
-6.55 0.99 -3.48 0.986 5 49

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 13 1 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 R1626L.
Neighbour residue Distance (Å) Observed variants
271 13 L271V,
266 10 L266H,
1569 13 A1569P,
1544 10 T1544P,
270 10 Q270K,
1627 6
1567 9 F1567L, F1567L, F1567L,
1624 7 V1624I,
1536 15
1538 8
1566 13
1568 9
1543 11 V1543L, V1543L, V1543A,
1602 9
1534 13
1542 8
1601 9 L1601H,
1575 14 C1575S, C1575S,
1600 12
1571 9 F1571C,
1572 13
1564 8
1570 13 p.1570_F1571insI, I1570V, p.I1570dup,
1599 9
1546 12 M1546T,
1545 7
1630 10 I1630V, I1630R,
1626 0 R1626C, R1626H, R1626P, R1626L,
267 11
1603 13 I1603F,
1625 6
1606 12 T1606I,
1560 12 L1560F, L1560F,
262 14 S262G,
1596 13 F1596I, F1596C,
1628 8
1632 12 R1632C, R1632H, R1632L
1539 11 C1539Y, C1539F,
1597 10 V1597M,
269 13
1620 11 T1620K, T1620M,
1535 13
1537 11
1565 12 L1565M,
1594 11 F1594S,
264 14
1591 14 W1591X,
1548 12 E1548K, G1548K,
1593 15 I1593M,
1595 10
265 14 A265V,
1619 10 P1619Q, P1619L, c.4856delC,
263 12 V263I,
1629 7 R1629G, R1629X, R1629Q,
1605 12 c.4813+2_4813+5dupTGGG, c.4813+3_4813+6dupGGGT, c.4813+5insTGGG, G1605C, G1605D,
1547 14 V1547L, V1547L,
1574 13 c.4719C>T, E1574K,
1563 11
1541 6
1592 15
1540 11
1617 12 p.F1617del,
1631 13 G1631D,
268 14 G268S,
1604 13 c.4810+3_4810+6dupGGGT, V1604M,
1622 5
1618 12
1621 10
1598 6 V1598A,
1561 12
1623 6 c.4867delC, R1623X, R1623Q, R1623L,