Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32516 | 97771;97772;97773 | chr2:178541531;178541530;178541529 | chr2:179406258;179406257;179406256 |
| N2AB | 30875 | 92848;92849;92850 | chr2:178541531;178541530;178541529 | chr2:179406258;179406257;179406256 |
| N2A | 29948 | 90067;90068;90069 | chr2:178541531;178541530;178541529 | chr2:179406258;179406257;179406256 |
| N2B | 23451 | 70576;70577;70578 | chr2:178541531;178541530;178541529 | chr2:179406258;179406257;179406256 |
| Novex-1 | 23576 | 70951;70952;70953 | chr2:178541531;178541530;178541529 | chr2:179406258;179406257;179406256 |
| Novex-2 | 23643 | 71152;71153;71154 | chr2:178541531;178541530;178541529 | chr2:179406258;179406257;179406256 |
| Novex-3 | None | None | chr2:None | chr2:None |
Information
Reported SAVs
| SNV | RS | DUET |
PolyPhen-2 |
Condel |
Rhapsody |
REVEL |
MVP |
Source |
MAF |
Disease |
Zygosity |
Site annotation |
mCSM PPI |
Predicted PPI site |
Comments |
AFR |
AMR |
AMS |
ASJ |
EAS |
EUR |
FIN |
MDE |
NFE |
SAS |
OTH |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/I | rs1374106457  |
-0.593 | 0.985 | N | 0.649 | 0.357 | 0.364926071151 | gnomAD-2.1.1 | 4.05E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.94E-06 | 0 |
| M/I | rs1374106457 |
-0.593 | 0.985 | N | 0.649 | 0.357 | 0.364926071151 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| M/I | rs1374106457 |
-0.593 | 0.985 | N | 0.649 | 0.357 | 0.364926071151 | gnomAD-4.0.0 | 2.56537E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.79134E-06 | 0 | 0 |
| M/K | rs557550837 |
-1.134 | 0.994 | N | 0.769 | 0.619 | 0.644471222209 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.29E-05 | None | 0 | 0 | 0 |
| M/K | rs557550837 |
-1.134 | 0.994 | N | 0.769 | 0.619 | 0.644471222209 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.06697E-04 | 0 |
| M/K | rs557550837 |
-1.134 | 0.994 | N | 0.769 | 0.619 | 0.644471222209 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 1E-03 | None |
| M/K | rs557550837 |
-1.134 | 0.994 | N | 0.769 | 0.619 | 0.644471222209 | gnomAD-4.0.0 | 2.47993E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 4.40131E-05 | 0 |
| M/T | rs557550837 |
None | 0.994 | N | 0.767 | 0.553 | 0.76991710822 | gnomAD-4.0.0 | 6.84628E-07 | None | None | None | None | N | None | 2.99025E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
Saturation Mutagenesis
SAV |
AlphaMissense (IC) |
AlphaMissense Class (IC) |
AlphaMissense (N2AB) |
AlphaMissense Class (N2AB) |
mCSM |
mCSM class |
PolyPhen-2 |
PolyPhen-2 Class |
Rhapsody |
Rhapsody Class |
Condel |
Condel Score |
Site annotation |
mCSM PPI |
Predicted PPI site |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.7851 | likely_pathogenic | 0.7939 | pathogenic | -2.044 | Highly Destabilizing | 0.989 | D | 0.689 | prob.neutral | None | None | None | None | N |
| M/C | 0.83 | likely_pathogenic | 0.8418 | pathogenic | -2.572 | Highly Destabilizing | 1.0 | D | 0.77 | deleterious | None | None | None | None | N |
| M/D | 0.9959 | likely_pathogenic | 0.9966 | pathogenic | -2.399 | Highly Destabilizing | 0.999 | D | 0.823 | deleterious | None | None | None | None | N |
| M/E | 0.9605 | likely_pathogenic | 0.9703 | pathogenic | -2.209 | Highly Destabilizing | 0.999 | D | 0.773 | deleterious | None | None | None | None | N |
| M/F | 0.6493 | likely_pathogenic | 0.6922 | pathogenic | -0.783 | Destabilizing | 0.999 | D | 0.713 | prob.delet. | None | None | None | None | N |
| M/G | 0.9545 | likely_pathogenic | 0.958 | pathogenic | -2.457 | Highly Destabilizing | 0.995 | D | 0.753 | deleterious | None | None | None | None | N |
| M/H | 0.9737 | likely_pathogenic | 0.9796 | pathogenic | -2.112 | Highly Destabilizing | 1.0 | D | 0.775 | deleterious | None | None | None | None | N |
| M/I | 0.5433 | ambiguous | 0.5398 | ambiguous | -0.873 | Destabilizing | 0.985 | D | 0.649 | neutral | N | 0.385193738 | None | None | N |
| M/K | 0.9108 | likely_pathogenic | 0.9224 | pathogenic | -1.39 | Destabilizing | 0.994 | D | 0.769 | deleterious | N | 0.482517145 | None | None | N |
| M/L | 0.3453 | ambiguous | 0.3547 | ambiguous | -0.873 | Destabilizing | 0.927 | D | 0.434 | neutral | N | 0.434969197 | None | None | N |
| M/N | 0.9552 | likely_pathogenic | 0.9621 | pathogenic | -1.769 | Destabilizing | 0.999 | D | 0.795 | deleterious | None | None | None | None | N |
| M/P | 0.9975 | likely_pathogenic | 0.9976 | pathogenic | -1.245 | Destabilizing | 0.999 | D | 0.798 | deleterious | None | None | None | None | N |
| M/Q | 0.8112 | likely_pathogenic | 0.8438 | pathogenic | -1.547 | Destabilizing | 0.999 | D | 0.734 | prob.delet. | None | None | None | None | N |
| M/R | 0.92 | likely_pathogenic | 0.9279 | pathogenic | -1.448 | Destabilizing | 0.998 | D | 0.807 | deleterious | N | 0.482517145 | None | None | N |
| M/S | 0.8846 | likely_pathogenic | 0.9046 | pathogenic | -2.253 | Highly Destabilizing | 0.995 | D | 0.75 | deleterious | None | None | None | None | N |
| M/T | 0.8332 | likely_pathogenic | 0.8613 | pathogenic | -1.946 | Destabilizing | 0.994 | D | 0.767 | deleterious | N | 0.47065386 | None | None | N |
| M/V | 0.2073 | likely_benign | 0.2154 | benign | -1.245 | Destabilizing | 0.985 | D | 0.547 | neutral | N | 0.349136937 | None | None | N |
| M/W | 0.9731 | likely_pathogenic | 0.9786 | pathogenic | -1.128 | Destabilizing | 1.0 | D | 0.749 | deleterious | None | None | None | None | N |
| M/Y | 0.9491 | likely_pathogenic | 0.9589 | pathogenic | -1.056 | Destabilizing | 0.999 | D | 0.815 | deleterious | None | None | None | None | N |
Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.