SCN5A Variant V1597M
Summary of observed carriers, functional annotations, and structural context for SCN5A V1597M. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
15%
1/16 effective observations
Estimated BrS1 penetrance
5%
0/16 effective observations
Total carriers
6
0 BrS1 · 1 LQT3 · 5 unaffected
Variant features alone are equivalent to phenotyping 0 individuals for Brugada syndrome and 0 individuals for LQT3.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
|---|---|---|---|---|---|
| -2.51 | 0.981 | 0.99 | 0.942 | 2 | 15 |
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 |
|---|---|---|---|---|---|---|---|
| 24606995 | 2014 | 1 | 1 | 0 | 0 | ||
| Literature, cohort, and gnomAD | – | 6 | 5 | 1 | 0 | – | |
| Variant features alone | – | 15 | 15 | 0 | 0 | – | – |
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) |
|---|---|---|---|---|---|---|
| 24606995 | 2014 |
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 |
|---|---|---|
| 1569 | 15 | A1569P, |
| 1627 | 13 | |
| 1586 | 11 | |
| 1624 | 11 | V1624I, |
| 1538 | 14 | |
| 1568 | 12 | |
| 1587 | 11 | F1587V, |
| 1602 | 9 | |
| 1601 | 6 | L1601H, |
| 1575 | 10 | C1575S, C1575S, |
| 1600 | 5 | |
| 1571 | 11 | F1571C, |
| 1572 | 12 | |
| 1599 | 6 | |
| 1630 | 15 | I1630V, I1630R, |
| 1626 | 10 | R1626P, R1626C, R1626H, R1626L, |
| 1603 | 10 | I1603F, |
| 1625 | 6 | |
| 1606 | 14 | T1606I, |
| 1576 | 14 | |
| 1596 | 5 | F1596C, F1596I |
| 1628 | 10 | |
| 1589 | 13 | |
| 1632 | 13 | R1632L, R1632C, R1632H, |
| 1597 | 0 | V1597M, |
| 1620 | 14 | T1620K, T1620M, |
| 1573 | 14 | |
| 1594 | 6 | F1594S, |
| 1588 | 15 | T1588I, |
| 1591 | 12 | W1591X, |
| 1593 | 7 | I1593M, |
| 1595 | 7 | |
| 1619 | 14 | P1619Q, c.4856delC, P1619L, |
| 1629 | 9 | R1629X, R1629Q, R1629G, |
| 1605 | 13 | c.4813+5insTGGG, c.4813+2_4813+5dupTGGG, G1605D, c.4813+3_4813+6dupGGGT, G1605C, |
| 1574 | 12 | E1574K, c.4719C>T, |
| 1541 | 15 | |
| 1616 | 14 | |
| 1607 | 15 | |
| 1592 | 10 | |
| 1578 | 13 | c.4732_4733dupAA, |
| 1617 | 10 | p.F1617del, |
| 1631 | 15 | G1631D, |
| 1590 | 11 | |
| 1604 | 10 | c.4810+3_4810+6dupGGGT, V1604M, |
| 1622 | 9 | |
| 1618 | 12 | |
| 1621 | 10 | |
| 1579 | 13 | L1579fsX53, |
| 1598 | 4 | V1598A, |
| 1623 | 13 | R1623Q, c.4867delC, R1623X, R1623L, |