T630M Summary

SCN5A T630M was found in 2 papers (see below) with a total of 14 carriers: 0 had BrS1, 0 had LQT3, and 1 had other disease. T630M is present in 14 out of 206444 alleles in gnomAD (minor allele frequency of 0.006782%). T630M has been functionally characterized in 0 papers. Other variants at the same resdue are T630A .T630K .T630M .T630P .T630R .T630S . Given the functional data available, we estimate this variant has "Mild_LOF" in vitro character. (LOF and GOF denote loss-of-function and gain-of-function, respectively). This residue is located in a Non_Hotspot region for BrS1 and in a Non_Hotspot region for Long QT syndrome.

T630M Reported Clinical Data

PMID Year Unaffected BrS LQT3 Other Other disease
2461399520140001irritable bowel syndrome
3005997320180020
Summary totals might not agree with the literature table because of duplicate patients, which were excluded from the total counts.

T630M 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
24613995 2014 HEK 68.9 1.5 1.3 75.8

T630M 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 0.044 -2.27 possiblydamaging 0.943 3.571 0.71 -4 0.543

T630M 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
615 14.7 G615E
616 14.2
617 13.7
618 13.2 L618F
619 12.6 L619F
620 12 R620C R620H
621 11.4
622 10.7
623 10.1
624 9.3 L624Q
625 8.5 E625D E625D
626 7.6
627 6.6 P627L
628 5.4
629 3.8
631 3.8
632 5.4 T632M
633 6.6
634 7.6 S634L
635 8.5
636 9.3
637 10.1
638 10.7
639 11.4 G639R G639R
640 12 P640A
641 12.6
642 13.2
643 13.7
644 14.2
645 14.7