Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 4001 | 12226;12227;12228 | chr2:178741232;178741231;178741230 | chr2:179605959;179605958;179605957 |
| N2AB | 3684 | 11275;11276;11277 | chr2:178741232;178741231;178741230 | chr2:179605959;179605958;179605957 |
| N2A | None | None | chr2:None | chr2:None |
| N2B | 3638 | 11137;11138;11139 | chr2:178741232;178741231;178741230 | chr2:179605959;179605958;179605957 |
| Novex-1 | 3763 | 11512;11513;11514 | chr2:178741232;178741231;178741230 | chr2:179605959;179605958;179605957 |
| Novex-2 | 3830 | 11713;11714;11715 | chr2:178741232;178741231;178741230 | chr2:179605959;179605958;179605957 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/R | rs1292211761  |
-1.309 | 0.863 | N | 0.669 | 0.254 | None | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| P/R | rs1292211761 |
-1.309 | 0.863 | N | 0.669 | 0.254 | None | gnomAD-4.0.0 | 4.77625E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 4.29812E-05 | 0 |
| P/T | rs1320141997 |
-2.336 | 0.27 | N | 0.485 | 0.16 | None | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| P/T | rs1320141997 |
-2.336 | 0.27 | N | 0.485 | 0.16 | None | gnomAD-4.0.0 | 1.592E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43271E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.3353 | likely_benign | 0.3184 | benign | -1.799 | Destabilizing | 0.139 | N | 0.426 | neutral | N | 0.437405651 | None | None | N |
| P/C | 0.8206 | likely_pathogenic | 0.8052 | pathogenic | -1.814 | Destabilizing | 0.007 | N | 0.513 | neutral | None | None | None | None | N |
| P/D | 0.99 | likely_pathogenic | 0.991 | pathogenic | -3.072 | Highly Destabilizing | 0.704 | D | 0.587 | neutral | None | None | None | None | N |
| P/E | 0.9631 | likely_pathogenic | 0.9681 | pathogenic | -3.016 | Highly Destabilizing | 0.704 | D | 0.547 | neutral | None | None | None | None | N |
| P/F | 0.9695 | likely_pathogenic | 0.9752 | pathogenic | -1.306 | Destabilizing | 0.704 | D | 0.695 | prob.neutral | None | None | None | None | N |
| P/G | 0.9097 | likely_pathogenic | 0.8987 | pathogenic | -2.147 | Highly Destabilizing | 0.329 | N | 0.528 | neutral | None | None | None | None | N |
| P/H | 0.9226 | likely_pathogenic | 0.9413 | pathogenic | -1.615 | Destabilizing | 0.975 | D | 0.64 | neutral | D | 0.61433118 | None | None | N |
| P/I | 0.6829 | likely_pathogenic | 0.6919 | pathogenic | -0.895 | Destabilizing | 0.013 | N | 0.467 | neutral | None | None | None | None | N |
| P/K | 0.968 | likely_pathogenic | 0.9768 | pathogenic | -1.616 | Destabilizing | 0.704 | D | 0.545 | neutral | None | None | None | None | N |
| P/L | 0.462 | ambiguous | 0.4694 | ambiguous | -0.895 | Destabilizing | 0.002 | N | 0.425 | neutral | N | 0.453821774 | None | None | N |
| P/M | 0.8364 | likely_pathogenic | 0.8312 | pathogenic | -0.959 | Destabilizing | 0.893 | D | 0.667 | neutral | None | None | None | None | N |
| P/N | 0.9624 | likely_pathogenic | 0.9658 | pathogenic | -1.781 | Destabilizing | 0.704 | D | 0.637 | neutral | None | None | None | None | N |
| P/Q | 0.9081 | likely_pathogenic | 0.9197 | pathogenic | -1.937 | Destabilizing | 0.944 | D | 0.655 | neutral | None | None | None | None | N |
| P/R | 0.911 | likely_pathogenic | 0.9299 | pathogenic | -1.11 | Destabilizing | 0.863 | D | 0.669 | neutral | N | 0.501024454 | None | None | N |
| P/S | 0.6804 | likely_pathogenic | 0.69 | pathogenic | -2.175 | Highly Destabilizing | 0.01 | N | 0.415 | neutral | N | 0.492999997 | None | None | N |
| P/T | 0.413 | ambiguous | 0.4128 | ambiguous | -2.017 | Highly Destabilizing | 0.27 | N | 0.485 | neutral | N | 0.479420685 | None | None | N |
| P/V | 0.5338 | ambiguous | 0.5357 | ambiguous | -1.168 | Destabilizing | 0.013 | N | 0.408 | neutral | None | None | None | None | N |
| P/W | 0.9925 | likely_pathogenic | 0.9941 | pathogenic | -1.627 | Destabilizing | 0.995 | D | 0.631 | neutral | None | None | None | None | N |
| P/Y | 0.9787 | likely_pathogenic | 0.9838 | pathogenic | -1.328 | Destabilizing | 0.981 | D | 0.699 | prob.neutral | 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.