Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16797 | 50614;50615;50616 | chr2:178611920;178611919;178611918 | chr2:179476647;179476646;179476645 |
| N2AB | 15156 | 45691;45692;45693 | chr2:178611920;178611919;178611918 | chr2:179476647;179476646;179476645 |
| N2A | 14229 | 42910;42911;42912 | chr2:178611920;178611919;178611918 | chr2:179476647;179476646;179476645 |
| N2B | 7732 | 23419;23420;23421 | chr2:178611920;178611919;178611918 | chr2:179476647;179476646;179476645 |
| Novex-1 | 7857 | 23794;23795;23796 | chr2:178611920;178611919;178611918 | chr2:179476647;179476646;179476645 |
| Novex-2 | 7924 | 23995;23996;23997 | chr2:178611920;178611919;178611918 | chr2:179476647;179476646;179476645 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/C | rs1015961035  |
None | 1.0 | D | 0.768 | 0.507 | None | gnomAD-4.0.0 | 6.16266E-06 | None | None | None | None | I | None | 2.99258E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 6.29914E-06 | 0 | 1.65837E-05 |
| R/H | rs200835354 |
-0.584 | 1.0 | N | 0.744 | 0.396 | None | gnomAD-2.1.1 | 1.07601E-04 | None | None | None | None | I | None | 2.06919E-04 | 5.68E-05 | None | 0 | 0 | None | 0 | None | 4.40458E-04 | 8.64E-05 | 1.40964E-04 |
| R/H | rs200835354 |
-0.584 | 1.0 | N | 0.744 | 0.396 | None | gnomAD-3.1.2 | 1.31593E-04 | None | None | None | None | I | None | 2.17202E-04 | 1.31079E-04 | 0 | 0 | 0 | None | 4.71342E-04 | 0 | 5.89E-05 | 0 | 0 |
| R/H | rs200835354 |
-0.584 | 1.0 | N | 0.744 | 0.396 | None | gnomAD-4.0.0 | 1.01712E-04 | None | None | None | None | I | None | 2.00401E-04 | 6.6807E-05 | None | 0 | 2.24085E-05 | None | 4.69043E-04 | 3.29707E-04 | 9.15886E-05 | 0 | 6.41108E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.9369 | likely_pathogenic | 0.9293 | pathogenic | 0.097 | Stabilizing | 0.999 | D | 0.622 | neutral | None | None | None | None | I |
| R/C | 0.7932 | likely_pathogenic | 0.7542 | pathogenic | -0.227 | Destabilizing | 1.0 | D | 0.768 | deleterious | D | 0.626394952 | None | None | I |
| R/D | 0.9704 | likely_pathogenic | 0.9612 | pathogenic | -0.298 | Destabilizing | 1.0 | D | 0.702 | prob.neutral | None | None | None | None | I |
| R/E | 0.9128 | likely_pathogenic | 0.8884 | pathogenic | -0.257 | Destabilizing | 0.999 | D | 0.667 | neutral | None | None | None | None | I |
| R/F | 0.9637 | likely_pathogenic | 0.9588 | pathogenic | -0.236 | Destabilizing | 1.0 | D | 0.755 | deleterious | None | None | None | None | I |
| R/G | 0.897 | likely_pathogenic | 0.8772 | pathogenic | -0.036 | Destabilizing | 1.0 | D | 0.611 | neutral | N | 0.476717961 | None | None | I |
| R/H | 0.5352 | ambiguous | 0.4797 | ambiguous | -0.559 | Destabilizing | 1.0 | D | 0.744 | deleterious | N | 0.47600419 | None | None | I |
| R/I | 0.8728 | likely_pathogenic | 0.8693 | pathogenic | 0.401 | Stabilizing | 1.0 | D | 0.754 | deleterious | None | None | None | None | I |
| R/K | 0.4405 | ambiguous | 0.4041 | ambiguous | -0.118 | Destabilizing | 0.998 | D | 0.619 | neutral | None | None | None | None | I |
| R/L | 0.825 | likely_pathogenic | 0.8133 | pathogenic | 0.401 | Stabilizing | 1.0 | D | 0.611 | neutral | N | 0.480474146 | None | None | I |
| R/M | 0.9212 | likely_pathogenic | 0.909 | pathogenic | -0.081 | Destabilizing | 1.0 | D | 0.71 | prob.delet. | None | None | None | None | I |
| R/N | 0.953 | likely_pathogenic | 0.9494 | pathogenic | -0.064 | Destabilizing | 1.0 | D | 0.7 | prob.neutral | None | None | None | None | I |
| R/P | 0.9706 | likely_pathogenic | 0.969 | pathogenic | 0.318 | Stabilizing | 1.0 | D | 0.702 | prob.neutral | D | 0.583275524 | None | None | I |
| R/Q | 0.5357 | ambiguous | 0.4911 | ambiguous | -0.077 | Destabilizing | 1.0 | D | 0.691 | prob.neutral | None | None | None | None | I |
| R/S | 0.9514 | likely_pathogenic | 0.9446 | pathogenic | -0.204 | Destabilizing | 1.0 | D | 0.635 | neutral | N | 0.475397371 | None | None | I |
| R/T | 0.9022 | likely_pathogenic | 0.889 | pathogenic | -0.06 | Destabilizing | 1.0 | D | 0.647 | neutral | None | None | None | None | I |
| R/V | 0.8859 | likely_pathogenic | 0.8778 | pathogenic | 0.318 | Stabilizing | 1.0 | D | 0.737 | prob.delet. | None | None | None | None | I |
| R/W | 0.8169 | likely_pathogenic | 0.7729 | pathogenic | -0.451 | Destabilizing | 1.0 | D | 0.785 | deleterious | None | None | None | None | I |
| R/Y | 0.9107 | likely_pathogenic | 0.9009 | pathogenic | -0.039 | Destabilizing | 1.0 | D | 0.722 | prob.delet. | 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.