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
Variant features alone are equivalent to phenotyping 2 individuals for Brugada syndrome and 1 individuals for LQT3.
In silico 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
| 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.
Nearby variants
Neighbouring residues within 15 Ångström provide structural context. Variants listed in the right-most column have been observed clinically or in gnomAD.
| Neighbour residue | Distance (Å) | Observed variants |
|---|---|---|
| 271 | 7 | L271V, |
| 266 | 9 | L266H, |
| 1544 | 12 | T1544P, |
| 270 | 5 | Q270K, |
| 1627 | 7 | |
| 1567 | 14 | F1567L, |
| 1624 | 6 | V1624I, |
| 355 | 13 | F355C, F355I, |
| 1549 | 14 | |
| 1538 | 14 | |
| 1568 | 14 | |
| 356 | 15 | D356N, |
| 1543 | 14 | V1543L, V1543A, |
| 1602 | 12 | |
| 1542 | 11 | |
| 1601 | 11 | L1601H, |
| 1557 | 14 | I1557V, |
| 1613 | 14 | Q1613L, Q1613H, |
| 1564 | 11 | |
| 1599 | 14 | |
| 1546 | 12 | M1546T, |
| 1545 | 7 | |
| 1630 | 14 | I1630V, I1630R, |
| 1626 | 6 | R1626H, R1626P, R1626C, R1626L, |
| 267 | 8 | |
| 1550 | 14 | |
| 1625 | 8 | |
| 1606 | 14 | T1606I, |
| 1560 | 12 | 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 | T1620M, T1620K, |
| 1565 | 15 | L1565M, |
| 275 | 13 | N275K, |
| 1594 | 15 | F1594S, |
| 264 | 13 | |
| 1548 | 10 | G1548K, E1548K, |
| 265 | 12 | A265V, |
| 1619 | 5 | P1619Q, P1619L, c.4856delC, |
| 358 | 14 | |
| 263 | 12 | V263I, |
| 1629 | 13 | R1629Q, R1629G, R1629X, |
| 1605 | 12 | c.4813+5insTGGG, G1605C, G1605D, c.4813+2_4813+5dupTGGG, c.4813+3_4813+6dupGGGT, |
| 1547 | 13 | 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, R1623Q, R1623L, R1623X, |