SCN5A Variant M1487L

Summary of observed carriers, functional annotations, and structural context for SCN5A M1487L. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

40%

3/14 effective observations

Estimated BrS1 penetrance

3%

0/14 effective observations

Total carriers

4

0 BrS1 · 1 LQT3 · 3 unaffected

M1487L is present in 3 alleles in gnomAD. This residue resides in a Non_Hotspot region for Brugada syndrome and a Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 0 individuals for Brugada syndrome and 2 individuals for LQT3.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density BrS (%) Penetrance Density LQT3 (%)
-2.76 0.002 2.96 0.815 1 71

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
24631775 2014 1 0 0 1 SIDS
19716085 2009 1 1 0 0
30059973 2018 1 1 0 0
Literature, cohort, and gnomAD – 4 3 1 0 –
Variant features alone – 15 13 2 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)
30059973 2018
24631775 2014
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 M1487L.
Neighbour residue Distance (Å) Observed variants
1773 14
943 12 S943N,
1486 7 p.F1486del, F1486L,
1472 15 p.N1472del, N1472S,
1777 14 V1777L, V1777M,
1485 7
1487 0 M1487K, M1487L,
1492 10
1477 13 K1477N,
1491 10 Q1491H,
1471 13
1493 12 p.K1493del, K1493R, K1493X
1478 8 K1478E,
1776 15
944 14
1495 14 Y1495S,
1479 13
1496 14
1474 10
1481 13 G1481V, G1481E, G1481R,
1488 5 T1488R,
1780 14 E1780G,
1482 10
1476 14 Q1476X, Q1476R,
1484 6
1490 10
1475 10 Q1475L, p.Q1475NfsX6,
1483 8 Q1483H,
1489 6 E1489D,