Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20679 | 62260;62261;62262 | chr2:178589690;178589689;178589688 | chr2:179454417;179454416;179454415 |
| N2AB | 19038 | 57337;57338;57339 | chr2:178589690;178589689;178589688 | chr2:179454417;179454416;179454415 |
| N2A | 18111 | 54556;54557;54558 | chr2:178589690;178589689;178589688 | chr2:179454417;179454416;179454415 |
| N2B | 11614 | 35065;35066;35067 | chr2:178589690;178589689;178589688 | chr2:179454417;179454416;179454415 |
| Novex-1 | 11739 | 35440;35441;35442 | chr2:178589690;178589689;178589688 | chr2:179454417;179454416;179454415 |
| Novex-2 | 11806 | 35641;35642;35643 | chr2:178589690;178589689;178589688 | chr2:179454417;179454416;179454415 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/E | rs878956804  |
-0.105 | 0.002 | N | 0.176 | 0.085 | 0.12205267543 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.58E-05 | None | 0 | None | 0 | 0 | 0 |
| D/E | rs878956804 |
-0.105 | 0.002 | N | 0.176 | 0.085 | 0.12205267543 | gnomAD-4.0.0 | 4.10583E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.52131E-05 | None | 0 | 0 | 3.59831E-06 | 0 | 1.65673E-05 |
| D/Y | None | None | 0.975 | N | 0.629 | 0.438 | 0.698802292485 | gnomAD-4.0.0 | 4.77537E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.55155E-05 | None | 0 | 0 | 2.85938E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.6677 | likely_pathogenic | 0.5047 | ambiguous | -0.082 | Destabilizing | 0.477 | N | 0.461 | neutral | N | 0.506493726 | None | None | N |
| D/C | 0.9703 | likely_pathogenic | 0.9287 | pathogenic | -0.127 | Destabilizing | 0.995 | D | 0.631 | neutral | None | None | None | None | N |
| D/E | 0.3287 | likely_benign | 0.1951 | benign | -0.275 | Destabilizing | 0.002 | N | 0.176 | neutral | N | 0.449965653 | None | None | N |
| D/F | 0.9582 | likely_pathogenic | 0.9273 | pathogenic | 0.631 | Stabilizing | 0.981 | D | 0.628 | neutral | None | None | None | None | N |
| D/G | 0.6793 | likely_pathogenic | 0.5107 | ambiguous | -0.42 | Destabilizing | 0.645 | D | 0.5 | neutral | N | 0.466773655 | None | None | N |
| D/H | 0.8544 | likely_pathogenic | 0.7105 | pathogenic | 0.779 | Stabilizing | 0.98 | D | 0.534 | neutral | N | 0.484930817 | None | None | N |
| D/I | 0.9344 | likely_pathogenic | 0.8637 | pathogenic | 0.804 | Stabilizing | 0.945 | D | 0.643 | neutral | None | None | None | None | N |
| D/K | 0.8635 | likely_pathogenic | 0.7128 | pathogenic | 0.269 | Stabilizing | 0.547 | D | 0.472 | neutral | None | None | None | None | N |
| D/L | 0.8838 | likely_pathogenic | 0.8028 | pathogenic | 0.804 | Stabilizing | 0.894 | D | 0.629 | neutral | None | None | None | None | N |
| D/M | 0.9545 | likely_pathogenic | 0.909 | pathogenic | 0.829 | Stabilizing | 0.995 | D | 0.612 | neutral | None | None | None | None | N |
| D/N | 0.4804 | ambiguous | 0.3345 | benign | -0.502 | Destabilizing | 0.645 | D | 0.485 | neutral | N | 0.497527526 | None | None | N |
| D/P | 0.994 | likely_pathogenic | 0.9883 | pathogenic | 0.534 | Stabilizing | 0.945 | D | 0.539 | neutral | None | None | None | None | N |
| D/Q | 0.7579 | likely_pathogenic | 0.5528 | ambiguous | -0.325 | Destabilizing | 0.809 | D | 0.466 | neutral | None | None | None | None | N |
| D/R | 0.8847 | likely_pathogenic | 0.7565 | pathogenic | 0.607 | Stabilizing | 0.894 | D | 0.573 | neutral | None | None | None | None | N |
| D/S | 0.5434 | ambiguous | 0.3607 | ambiguous | -0.667 | Destabilizing | 0.547 | D | 0.435 | neutral | None | None | None | None | N |
| D/T | 0.8053 | likely_pathogenic | 0.6316 | pathogenic | -0.362 | Destabilizing | 0.894 | D | 0.484 | neutral | None | None | None | None | N |
| D/V | 0.8159 | likely_pathogenic | 0.6825 | pathogenic | 0.534 | Stabilizing | 0.864 | D | 0.619 | neutral | N | 0.475269578 | None | None | N |
| D/W | 0.9876 | likely_pathogenic | 0.9714 | pathogenic | 0.879 | Stabilizing | 0.995 | D | 0.624 | neutral | None | None | None | None | N |
| D/Y | 0.8223 | likely_pathogenic | 0.6993 | pathogenic | 0.93 | Stabilizing | 0.975 | D | 0.629 | neutral | N | 0.484930817 | 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.