T632M Summary

SCN5A T632M was found in 4 papers (see below) with a total of 5 carriers: 2 had BrS1, 0 had LQT3, and 0 had other disease. T632M is present in 3 out of 244512 alleles in gnomAD (minor allele frequency of 0.001227%). T632M has been functionally characterized in 1 paper. Other variants at the same resdue are T632A .T632K .T632M .T632P .T632R .T632S . Given the functional data available, we estimate this variant has "Normal" in vitro character. (LOF and GOF denote loss-of-function and gain-of-function, respectively). This residue is located in a Mild_Hotspot region for BrS1 and in a Non_Hotspot region for Long QT syndrome.

T632M Reported Clinical Data

PMID Year Unaffected BrS LQT3 Other Other disease
2457316420140000
2012928320100100
2012928320100100
2932597620180100
Summary totals might not agree with the literature table because of duplicate patients, which were excluded from the total counts.

T632M Reported Functional Data

Peak current and late current are relative % to wildtype. V0.5 act/inact are the voltages at which half of the maximal current is reached during an activation and inactivation protocol, each is in units of mV and relative to wildtype.

PMID Year Cell type Peak current V0.5 act V0.5 inact Rec from inact Late current
24573164 2014 HEK 100 -2.33 NA

T632M Predictions

PROVEAN scores less than -2 are considered deleterious. REVEL scores higher than 0.5 or 0.75 is considered likely pathogenic (higher sensitivity with the former cutoff, higher specificity with the latter cutoff). A PolyPhen-2 score of 0.85 or greater is considered likely pathogenic. PAM scores reflect the chemistry difference between WT and variant amino acid (more negative being greater difference between the two). BLAST-PSSM reflects the evolutionary conservation of residue substitutions, more negative numbers indicate fewer observations of the specific substitution than is expected.

SIFT Sift Score PROVEAN Score Polyphen2 Polyphen2 Score eaRate blastPssm pamScore REVEL
Damaging 0.006 -2.64 probablydamaging 0.971 3.375 -0.17 -4 0.66

T632M has 30 neighbors within 15 ångströms that have been found in individuals.

A residue within a folded protein on average has nearest neighbors that fall roughly into two shells: a "nearest" neighbor around 5-6 angstroms and a second shell around 11 angstroms.

ResidueNumber Distance(Å) Variants
617 14.7
618 14.2 L618F
619 13.7 L619F
620 13.2 R620C R620H
621 12.6
622 12
623 11.4
624 10.7 L624Q
625 10.1 E625D E625D
626 9.3
627 8.5 P627L
628 7.6
629 6.6
630 5.4 T630M
631 3.8
633 3.8
634 5.4 S634L
635 6.6
636 7.6
637 8.5
638 9.3
639 10.1 G639R G639R
640 10.7 P640A
641 11.4
642 12
643 12.6
644 13.2
645 13.7
646 14.2
647 14.7 A647D A647S A647V