Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1512 | 4759;4760;4761 | chr2:178777531;178777530;178777529 | chr2:179642258;179642257;179642256 |
| N2AB | 1512 | 4759;4760;4761 | chr2:178777531;178777530;178777529 | chr2:179642258;179642257;179642256 |
| N2A | 1512 | 4759;4760;4761 | chr2:178777531;178777530;178777529 | chr2:179642258;179642257;179642256 |
| N2B | 1466 | 4621;4622;4623 | chr2:178777531;178777530;178777529 | chr2:179642258;179642257;179642256 |
| Novex-1 | 1466 | 4621;4622;4623 | chr2:178777531;178777530;178777529 | chr2:179642258;179642257;179642256 |
| Novex-2 | 1466 | 4621;4622;4623 | chr2:178777531;178777530;178777529 | chr2:179642258;179642257;179642256 |
| Novex-3 | 1512 | 4759;4760;4761 | chr2:178777531;178777530;178777529 | chr2:179642258;179642257;179642256 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | None | None | 0.996 | N | 0.473 | 0.364 | 0.381916209588 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.66327E-05 |
| T/I | rs375794484  |
-0.219 | 0.992 | N | 0.598 | 0.483 | None | gnomAD-2.1.1 | 1.6E-05 | None | None | None | None | I | None | 2.46214E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| T/I | rs375794484 |
-0.219 | 0.992 | N | 0.598 | 0.483 | None | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | I | None | 1.20662E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| T/I | rs375794484 |
-0.219 | 0.992 | N | 0.598 | 0.483 | None | 1000 genomes | 3.99361E-04 | None | None | None | None | I | None | 1.5E-03 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| T/I | rs375794484 |
-0.219 | 0.992 | N | 0.598 | 0.483 | None | gnomAD-4.0.0 | 7.68456E-06 | None | None | None | None | I | None | 1.01286E-04 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| T/P | None | None | 1.0 | D | 0.773 | 0.585 | 0.498065138572 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.27 | likely_benign | 0.2756 | benign | -0.941 | Destabilizing | 0.996 | D | 0.473 | neutral | N | 0.506074885 | None | None | I |
| T/C | 0.7113 | likely_pathogenic | 0.7221 | pathogenic | -0.888 | Destabilizing | 1.0 | D | 0.745 | deleterious | None | None | None | None | I |
| T/D | 0.9222 | likely_pathogenic | 0.9229 | pathogenic | -1.226 | Destabilizing | 1.0 | D | 0.772 | deleterious | None | None | None | None | I |
| T/E | 0.8083 | likely_pathogenic | 0.8082 | pathogenic | -1.167 | Destabilizing | 1.0 | D | 0.726 | prob.delet. | None | None | None | None | I |
| T/F | 0.6473 | likely_pathogenic | 0.6584 | pathogenic | -0.871 | Destabilizing | 1.0 | D | 0.793 | deleterious | None | None | None | None | I |
| T/G | 0.7366 | likely_pathogenic | 0.7439 | pathogenic | -1.243 | Destabilizing | 1.0 | D | 0.688 | prob.neutral | None | None | None | None | I |
| T/H | 0.6911 | likely_pathogenic | 0.6826 | pathogenic | -1.481 | Destabilizing | 1.0 | D | 0.761 | deleterious | None | None | None | None | I |
| T/I | 0.3084 | likely_benign | 0.3084 | benign | -0.207 | Destabilizing | 0.992 | D | 0.598 | neutral | N | 0.508634816 | None | None | I |
| T/K | 0.6698 | likely_pathogenic | 0.6551 | pathogenic | -0.92 | Destabilizing | 1.0 | D | 0.752 | deleterious | None | None | None | None | I |
| T/L | 0.2217 | likely_benign | 0.2275 | benign | -0.207 | Destabilizing | 0.994 | D | 0.506 | neutral | None | None | None | None | I |
| T/M | 0.1694 | likely_benign | 0.1747 | benign | 0.023 | Stabilizing | 1.0 | D | 0.764 | deleterious | None | None | None | None | I |
| T/N | 0.4465 | ambiguous | 0.4566 | ambiguous | -1.158 | Destabilizing | 1.0 | D | 0.709 | prob.delet. | N | 0.510424765 | None | None | I |
| T/P | 0.8579 | likely_pathogenic | 0.8642 | pathogenic | -0.42 | Destabilizing | 1.0 | D | 0.773 | deleterious | D | 0.615111744 | None | None | I |
| T/Q | 0.5782 | likely_pathogenic | 0.5752 | pathogenic | -1.301 | Destabilizing | 1.0 | D | 0.789 | deleterious | None | None | None | None | I |
| T/R | 0.5382 | ambiguous | 0.5289 | ambiguous | -0.7 | Destabilizing | 1.0 | D | 0.787 | deleterious | None | None | None | None | I |
| T/S | 0.3105 | likely_benign | 0.3192 | benign | -1.351 | Destabilizing | 0.998 | D | 0.441 | neutral | N | 0.502403187 | None | None | I |
| T/V | 0.2455 | likely_benign | 0.2524 | benign | -0.42 | Destabilizing | 0.813 | D | 0.35 | neutral | None | None | None | None | I |
| T/W | 0.8824 | likely_pathogenic | 0.8851 | pathogenic | -0.859 | Destabilizing | 1.0 | D | 0.761 | deleterious | None | None | None | None | I |
| T/Y | 0.7198 | likely_pathogenic | 0.7218 | pathogenic | -0.577 | Destabilizing | 1.0 | D | 0.787 | deleterious | None | None | None | None | I |
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.