T512I Summary

SCN5A T512I was found in 3 papers (see below) with a total of 3 carriers: 1 had BrS1, 0 had LQT3, and 2 had other disease. T512I is present in 1 out of 229040 alleles in gnomAD (minor allele frequency of 0.000437%). T512I has been functionally characterized in 1 paper. Other variants at the same resdue are T512A .T512I .T512N .T512P .T512S .T512S . 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.

T512I Reported Clinical Data

PMID Year Unaffected BrS LQT3 Other Other disease
1256915920031001AV Block
1256915420030000
2755463220170101CM
Summary totals might not agree with the literature table because of duplicate patients, which were excluded from the total counts.

T512I 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
12569159 2003 HEK 100 -8.7 -7.5 NA

T512I 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
Tolerated 0.15 -0.56 benign 0.022 3.539 -0.83 -2 0.54

T512I 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
497 14.7
498 14.2
499 13.7
500 13.2
501 12.6
502 12
503 11.4
504 10.7 R504T
505 10.1
506 9.3 M506K
507 8.5
508 7.6
509 6.6
510 5.4
511 3.8
513 3.8 R513C
514 5.4 G514C
515 6.6
516 7.6
517 8.5
518 9.3
519 10.1
520 10.7 M520V
521 11.4 K521E
522 12
523 12.6 R523C R523H
524 13.2 S524Y
525 13.7
526 14.2 R526C R526H
527 14.7 G527R G527R