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

V1597M is present in 5 alleles in gnomAD. This residue resides in a Non_Hotspot region for Brugada syndrome and a Mild_Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 0 individuals for Brugada syndrome and 0 individuals for LQT3.

In silico predictors

Variant-level computational 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

Observed carriers by publication or cohort.
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.

Published electrophysiology measurements.
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.

Previously observed variants near V1597M.
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,