Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20788 | 62587;62588;62589 | chr2:178589363;178589362;178589361 | chr2:179454090;179454089;179454088 |
| N2AB | 19147 | 57664;57665;57666 | chr2:178589363;178589362;178589361 | chr2:179454090;179454089;179454088 |
| N2A | 18220 | 54883;54884;54885 | chr2:178589363;178589362;178589361 | chr2:179454090;179454089;179454088 |
| N2B | 11723 | 35392;35393;35394 | chr2:178589363;178589362;178589361 | chr2:179454090;179454089;179454088 |
| Novex-1 | 11848 | 35767;35768;35769 | chr2:178589363;178589362;178589361 | chr2:179454090;179454089;179454088 |
| Novex-2 | 11915 | 35968;35969;35970 | chr2:178589363;178589362;178589361 | chr2:179454090;179454089;179454088 |
| 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/K | None | None | 0.006 | N | 0.343 | 0.06 | 0.107399877778 | gnomAD-4.0.0 | 1.59205E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.77963E-05 | None | 0 | 0 | 0 | 0 | 0 |
| R/S | None | None | 0.477 | N | 0.644 | 0.175 | 0.149567049428 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.2186 | likely_benign | 0.2534 | benign | -0.156 | Destabilizing | 0.547 | D | 0.619 | neutral | None | None | None | None | N |
| R/C | 0.1036 | likely_benign | 0.1357 | benign | -0.418 | Destabilizing | 0.995 | D | 0.721 | prob.delet. | None | None | None | None | N |
| R/D | 0.4673 | ambiguous | 0.5232 | ambiguous | -0.051 | Destabilizing | 0.894 | D | 0.695 | prob.neutral | None | None | None | None | N |
| R/E | 0.251 | likely_benign | 0.2955 | benign | 0.016 | Stabilizing | 0.547 | D | 0.605 | neutral | None | None | None | None | N |
| R/F | 0.2897 | likely_benign | 0.337 | benign | -0.399 | Destabilizing | 0.981 | D | 0.717 | prob.delet. | None | None | None | None | N |
| R/G | 0.204 | likely_benign | 0.2377 | benign | -0.347 | Destabilizing | 0.645 | D | 0.637 | neutral | N | 0.482367971 | None | None | N |
| R/H | 0.0733 | likely_benign | 0.0811 | benign | -0.743 | Destabilizing | 0.945 | D | 0.685 | prob.neutral | None | None | None | None | N |
| R/I | 0.1169 | likely_benign | 0.136 | benign | 0.313 | Stabilizing | 0.945 | D | 0.729 | prob.delet. | None | None | None | None | N |
| R/K | 0.0811 | likely_benign | 0.0982 | benign | -0.233 | Destabilizing | 0.006 | N | 0.343 | neutral | N | 0.452821452 | None | None | N |
| R/L | 0.1316 | likely_benign | 0.1504 | benign | 0.313 | Stabilizing | 0.707 | D | 0.637 | neutral | None | None | None | None | N |
| R/M | 0.158 | likely_benign | 0.1926 | benign | -0.107 | Destabilizing | 0.993 | D | 0.683 | prob.neutral | N | 0.452489337 | None | None | N |
| R/N | 0.3258 | likely_benign | 0.365 | ambiguous | -0.071 | Destabilizing | 0.894 | D | 0.671 | neutral | None | None | None | None | N |
| R/P | 0.6444 | likely_pathogenic | 0.6765 | pathogenic | 0.177 | Stabilizing | 0.945 | D | 0.699 | prob.neutral | None | None | None | None | N |
| R/Q | 0.0814 | likely_benign | 0.0895 | benign | -0.166 | Destabilizing | 0.809 | D | 0.699 | prob.neutral | None | None | None | None | N |
| R/S | 0.2469 | likely_benign | 0.2843 | benign | -0.492 | Destabilizing | 0.477 | N | 0.644 | neutral | N | 0.456035116 | None | None | N |
| R/T | 0.109 | likely_benign | 0.128 | benign | -0.286 | Destabilizing | 0.864 | D | 0.692 | prob.neutral | N | 0.410894685 | None | None | N |
| R/V | 0.1495 | likely_benign | 0.1721 | benign | 0.177 | Stabilizing | 0.894 | D | 0.721 | prob.delet. | None | None | None | None | N |
| R/W | 0.1286 | likely_benign | 0.1551 | benign | -0.423 | Destabilizing | 0.993 | D | 0.693 | prob.neutral | N | 0.48262146 | None | None | N |
| R/Y | 0.2286 | likely_benign | 0.2796 | benign | -0.015 | Destabilizing | 0.981 | D | 0.717 | prob.delet. | 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.