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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

T632M is present in 3 alleles in gnomAD. This residue resides in a Mild_Hotspot region for Brugada syndrome and a Mild_Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 2 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 (%)
-2.64 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

Observed carriers by publication or cohort.
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.

Published electrophysiology measurements.
PubMed ID Year Cell Type Peak Current (% WT) V1/2 Activation (mV) V1/2 Inactivation (mV) Late/Persistent Current (% WT)
24573164 2014 HEK 100 -2.33
29325976 2018
20129283 2010
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.

Previously observed variants near T632M.
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,