SCN5A Variant T632M
Summary of observed carriers, functional annotations, and structural context for SCN5A T632M. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
9%
0/15 effective observations
Estimated BrS1 penetrance
31%
4/15 effective observations
Total carriers
5
2 BrS1 · 0 LQT3 · 3 unaffected
Variant features alone are equivalent to phenotyping 2 individuals for Brugada syndrome and 0 individuals for LQT3.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
|---|---|---|---|---|---|
| -2.64 | 0.971 | -0.17 | 0.66 | 37 | 20 |
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 | ||
| 20129283 | 2010 | 1 | 0 | 1 | 0 | ||
| 29325976 | 2018 | 1 | 0 | 1 | 0 | ||
| Literature, cohort, and gnomAD | – | 5 | 3 | 0 | 2 | – | |
| Variant features alone | – | 15 | 13 | 0 | 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 |
|---|---|---|
| 617 | 15 | |
| 618 | 14 | L618F, |
| 619 | 14 | L619F, |
| 620 | 13 | R620C, R620H, |
| 621 | 13 | |
| 622 | 12 | |
| 623 | 11 | M623T, |
| 624 | 11 | L624Q, |
| 625 | 10 | c.1872dupA, E625Q, E625D, |
| 626 | 9 | |
| 627 | 8 | P627L, |
| 628 | 8 | P628R, |
| 629 | 7 | D629Y, |
| 630 | 5 | T630M, |
| 631 | 4 | p.T631VfsX101, c.1890G>A, c.1890+5G>A, |
| 632 | 0 | T632M, |
| 633 | 4 | |
| 634 | 5 | S634W, S634L |
| 635 | 7 | |
| 636 | 8 | E636K, |
| 637 | 8 | P637L, |
| 638 | 9 | G638D, |
| 639 | 10 | G639A, G639R, |
| 640 | 11 | P640A, P640S, P640L, |
| 641 | 11 | |
| 642 | 12 | |
| 643 | 13 | |
| 644 | 13 | |
| 645 | 14 | |
| 646 | 14 | c.1936delC, p.Q646RfsX5, |
| 647 | 15 | A647V, A647D, A647S, |