SCN5A Variant R1623L

Summary of observed carriers, functional annotations, and structural context for SCN5A R1623L. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

55%

4/13 effective observations

Estimated BrS1 penetrance

19%

2/13 effective observations

Total carriers

3

0 BrS1 · 3 LQT3 · 0 unaffected

R1623L has not been reported in gnomAD. This residue resides in a Mild_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 (%)
-6.17 0.154 -3.65 0.92 29 39

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
10973849 2000 1 1 0 0
15840476 2005 1 1 0 0
27566755 2016 3 3 0 0
19716085 2009 1 1 0 0
Literature, cohort, and gnomAD – 3 0 3 0 –
Variant features alone – 15 12 1 2 – –

Totals may differ from individual publications due to duplicate patients removed during curation.

Functional data

Peak and late/persistent current values are relative to wild-type (100% indicates no change). V1/2 activation and inactivation denote the membrane potentials (mV) at which half-maximal current is achieved.

Published electrophysiology measurements.
PubMed ID Year Cell Type Peak Current (% WT) V1/2 Activation (mV) V1/2 Inactivation (mV) Late/Persistent Current (% WT)
10973849 2000
15840476 2005
27566755 2016
19716085 2009

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 R1623L.
Neighbour residue Distance (Å) Observed variants
271 7 L271V,
266 9 L266H,
1544 12 T1544P,
270 5 Q270K,
1627 7
1567 14 F1567L, F1567L, F1567L,
1624 6 V1624I,
355 13 F355I, F355C,
1549 14
1538 14
1568 14
356 15 D356N,
1543 14 V1543L, V1543L, V1543A,
1602 12
1542 11
1601 11 L1601H,
1557 14 I1557V,
1613 14 Q1613L, Q1613H, Q1613H,
1564 11
1599 14
1546 12 M1546T,
1545 7
1630 14 I1630V, I1630R
1626 6 R1626C, R1626H, R1626P, R1626L,
267 8
1550 14
1625 8
1606 14 T1606I,
1560 12 L1560F, L1560F,
262 15 S262G,
272 11
274 14 G274C,
273 10
1628 11
1597 13 V1597M,
392 13
389 13 Y389H, Y389X,
269 9
1620 5 T1620K, T1620M,
1565 15 L1565M,
275 13 N275K, N275K,
1594 15 F1594S,
264 13
1548 10 E1548K, G1548K,
265 12 A265V,
1619 5 P1619Q, P1619L, c.4856delC,
358 14
263 12 V263I,
1629 13 R1629G, R1629X, R1629Q,
1605 12 c.4813+2_4813+5dupTGGG, c.4813+3_4813+6dupGGGT, c.4813+5insTGGG, G1605C, G1605D,
1547 13 V1547L, V1547L,
1563 14
1541 11
1617 10 p.F1617del,
268 10 G268S,
1604 14 c.4810+3_4810+6dupGGGT, V1604M,
1622 6
1618 8
1621 7
1598 11 V1598A,
1561 13
1623 0 c.4867delC, R1623X, R1623Q, R1623L,