SCN5A Variant V1604M
Summary of observed carriers, functional annotations, and structural context for SCN5A V1604M. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
2%
0/19 effective observations
Estimated BrS1 penetrance
22%
4/19 effective observations
Total carriers
9
1 BrS1 · 0 LQT3 · 8 unaffected
Variant features alone are equivalent to phenotyping 3 individuals for Brugada syndrome and 0 individuals for LQT3.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
|---|---|---|---|---|---|
| -2.21 | 0.844 | 3.15 | 0.833 | 46 | 1 |
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 |
|---|---|---|---|---|---|---|---|
| 20129283 | 2010 | 1 | 0 | 1 | 0 | ||
| Literature, cohort, and gnomAD | – | 9 | 8 | 0 | 1 | – | |
| Variant features alone | – | 15 | 12 | 0 | 3 | – | – |
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.
| PubMed ID | Year | Cell Type | Peak Current (% WT) | V1/2 Activation (mV) | V1/2 Inactivation (mV) | Late/Persistent Current (% WT) |
|---|---|---|---|---|---|---|
| 20129283 | 2010 |
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 |
|---|---|---|
| 1600 | 7 | |
| 1571 | 15 | F1571C, |
| 1606 | 7 | T1606I, |
| 1610 | 8 | D1610G, |
| 1569 | 14 | A1569P, |
| 1612 | 13 | |
| 1615 | 13 | Y1615X, |
| 1572 | 13 | |
| 1564 | 14 | |
| 1596 | 12 | F1596I, F1596C, |
| 1605 | 4 | c.4813+2_4813+5dupTGGG, c.4813+3_4813+6dupGGGT, c.4813+5insTGGG, G1605C, G1605D, |
| 1611 | 11 | I1611V, |
| 1597 | 10 | V1597M, |
| 1616 | 7 | |
| 1607 | 7 | |
| 1599 | 9 | |
| 1620 | 14 | T1620K, T1620M, |
| 1568 | 12 | |
| 1617 | 6 | p.F1617del, |
| 1608 | 5 | |
| 1565 | 13 | L1565M, |
| 1604 | 0 | c.4810+3_4810+6dupGGGT, V1604M, |
| 1602 | 6 | |
| 1622 | 9 | |
| 1618 | 10 | |
| 1614 | 13 | |
| 1626 | 13 | R1626C, R1626H, R1626P, R1626L |
| 1601 | 5 | L1601H, |
| 1621 | 12 | |
| 1609 | 8 | S1609W, S1609L, |
| 1603 | 5 | I1603F, |
| 1598 | 10 | V1598A, |
| 1623 | 14 | c.4867delC, R1623X, R1623Q, R1623L, |
| 1619 | 11 | P1619Q, P1619L, c.4856delC, |
| 1625 | 13 | |
| 1613 | 10 | Q1613L, Q1613H, Q1613H, |