Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23679 | 71260;71261;71262 | chr2:178575097;178575096;178575095 | chr2:179439824;179439823;179439822 |
| N2AB | 22038 | 66337;66338;66339 | chr2:178575097;178575096;178575095 | chr2:179439824;179439823;179439822 |
| N2A | 21111 | 63556;63557;63558 | chr2:178575097;178575096;178575095 | chr2:179439824;179439823;179439822 |
| N2B | 14614 | 44065;44066;44067 | chr2:178575097;178575096;178575095 | chr2:179439824;179439823;179439822 |
| Novex-1 | 14739 | 44440;44441;44442 | chr2:178575097;178575096;178575095 | chr2:179439824;179439823;179439822 |
| Novex-2 | 14806 | 44641;44642;44643 | chr2:178575097;178575096;178575095 | chr2:179439824;179439823;179439822 |
| 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 | rs200144345  |
-0.723 | 0.997 | N | 0.466 | 0.224 | None | gnomAD-2.1.1 | 5.22477E-04 | None | None | None | None | N | None | 4.14E-05 | 2.84E-05 | None | 3.00388E-03 | 0 | None | 6.87308E-04 | None | 4.01E-05 | 6.73E-04 | 7.05617E-04 |
| R/K | rs200144345 |
-0.723 | 0.997 | N | 0.466 | 0.224 | None | gnomAD-3.1.2 | 4.07686E-04 | None | None | None | None | N | None | 7.24E-05 | 3.92927E-04 | 0 | 2.59366E-03 | 0 | None | 0 | 3.16456E-03 | 5.73648E-04 | 6.21633E-04 | 4.78469E-04 |
| R/K | rs200144345 |
-0.723 | 0.997 | N | 0.466 | 0.224 | None | gnomAD-4.0.0 | 5.92587E-04 | None | None | None | None | N | None | 6.66542E-05 | 1.33369E-04 | None | 2.83937E-03 | 0 | None | 6.25215E-05 | 1.32144E-03 | 6.26505E-04 | 6.91897E-04 | 7.206E-04 |
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 | 0.9231 | likely_pathogenic | 0.9381 | pathogenic | -0.734 | Destabilizing | 0.999 | D | 0.551 | neutral | None | None | None | None | N |
| R/C | 0.6773 | likely_pathogenic | 0.7538 | pathogenic | -0.63 | Destabilizing | 1.0 | D | 0.683 | prob.neutral | None | None | None | None | N |
| R/D | 0.9504 | likely_pathogenic | 0.9604 | pathogenic | -0.121 | Destabilizing | 1.0 | D | 0.675 | neutral | None | None | None | None | N |
| R/E | 0.8543 | likely_pathogenic | 0.8737 | pathogenic | 0.006 | Stabilizing | 0.999 | D | 0.579 | neutral | None | None | None | None | N |
| R/F | 0.9547 | likely_pathogenic | 0.9683 | pathogenic | -0.556 | Destabilizing | 1.0 | D | 0.675 | neutral | None | None | None | None | N |
| R/G | 0.842 | likely_pathogenic | 0.8795 | pathogenic | -1.06 | Destabilizing | 1.0 | D | 0.649 | neutral | N | 0.488945472 | None | None | N |
| R/H | 0.3106 | likely_benign | 0.3631 | ambiguous | -1.406 | Destabilizing | 1.0 | D | 0.668 | neutral | None | None | None | None | N |
| R/I | 0.8683 | likely_pathogenic | 0.8989 | pathogenic | 0.144 | Stabilizing | 1.0 | D | 0.685 | prob.neutral | N | 0.503290745 | None | None | N |
| R/K | 0.3616 | ambiguous | 0.4123 | ambiguous | -0.82 | Destabilizing | 0.997 | D | 0.466 | neutral | N | 0.463773645 | None | None | N |
| R/L | 0.8044 | likely_pathogenic | 0.8537 | pathogenic | 0.144 | Stabilizing | 1.0 | D | 0.649 | neutral | None | None | None | None | N |
| R/M | 0.8497 | likely_pathogenic | 0.8938 | pathogenic | -0.155 | Destabilizing | 1.0 | D | 0.659 | neutral | None | None | None | None | N |
| R/N | 0.9014 | likely_pathogenic | 0.9234 | pathogenic | -0.275 | Destabilizing | 1.0 | D | 0.673 | neutral | None | None | None | None | N |
| R/P | 0.9763 | likely_pathogenic | 0.9774 | pathogenic | -0.127 | Destabilizing | 1.0 | D | 0.64 | neutral | None | None | None | None | N |
| R/Q | 0.3567 | ambiguous | 0.4144 | ambiguous | -0.415 | Destabilizing | 1.0 | D | 0.663 | neutral | None | None | None | None | N |
| R/S | 0.9449 | likely_pathogenic | 0.9591 | pathogenic | -0.995 | Destabilizing | 1.0 | D | 0.687 | prob.neutral | N | 0.484426021 | None | None | N |
| R/T | 0.8311 | likely_pathogenic | 0.87 | pathogenic | -0.684 | Destabilizing | 1.0 | D | 0.683 | prob.neutral | N | 0.493313565 | None | None | N |
| R/V | 0.9067 | likely_pathogenic | 0.9266 | pathogenic | -0.127 | Destabilizing | 1.0 | D | 0.684 | prob.neutral | None | None | None | None | N |
| R/W | 0.5965 | likely_pathogenic | 0.677 | pathogenic | -0.228 | Destabilizing | 1.0 | D | 0.687 | prob.neutral | None | None | None | None | N |
| R/Y | 0.8294 | likely_pathogenic | 0.8727 | pathogenic | 0.074 | Stabilizing | 1.0 | D | 0.663 | 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.