Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2501 | 7726;7727;7728 | chr2:178773555;178773554;178773553 | chr2:179638282;179638281;179638280 |
| N2AB | 2501 | 7726;7727;7728 | chr2:178773555;178773554;178773553 | chr2:179638282;179638281;179638280 |
| N2A | 2501 | 7726;7727;7728 | chr2:178773555;178773554;178773553 | chr2:179638282;179638281;179638280 |
| N2B | 2455 | 7588;7589;7590 | chr2:178773555;178773554;178773553 | chr2:179638282;179638281;179638280 |
| Novex-1 | 2455 | 7588;7589;7590 | chr2:178773555;178773554;178773553 | chr2:179638282;179638281;179638280 |
| Novex-2 | 2455 | 7588;7589;7590 | chr2:178773555;178773554;178773553 | chr2:179638282;179638281;179638280 |
| Novex-3 | 2501 | 7726;7727;7728 | chr2:178773555;178773554;178773553 | chr2:179638282;179638281;179638280 |
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/G | rs781459488  |
-1.736 | 1.0 | D | 0.732 | 0.495 | 0.577469734466 | gnomAD-2.1.1 | 1.99E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.63345E-04 | None | 0 | 0 | 0 |
| R/G | rs781459488 |
-1.736 | 1.0 | D | 0.732 | 0.495 | 0.577469734466 | gnomAD-4.0.0 | 7.52513E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.15934E-04 | 1.65585E-05 |
| R/L | rs369559000 |
-0.11 | 1.0 | D | 0.732 | 0.576 | 0.705191603356 | gnomAD-2.1.1 | 3.98E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.45E-05 | None | 0 | None | 0 | 0 | 0 |
| R/L | rs369559000 |
-0.11 | 1.0 | D | 0.732 | 0.576 | 0.705191603356 | gnomAD-4.0.0 | 6.84104E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.52054E-05 | None | 0 | 0 | 0 | 0 | 0 |
| R/Q | rs369559000 |
-0.599 | 1.0 | N | 0.733 | 0.345 | None | gnomAD-2.1.1 | 3.59E-05 | None | None | None | None | N | None | 6.15E-05 | 1.15761E-04 | None | 0 | 0 | None | 0 | None | 0 | 3.53E-05 | 0 |
| R/Q | rs369559000 |
-0.599 | 1.0 | N | 0.733 | 0.345 | None | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/Q | rs369559000 |
-0.599 | 1.0 | N | 0.733 | 0.345 | None | gnomAD-4.0.0 | 4.15153E-05 | None | None | None | None | N | None | 2.67051E-05 | 8.33778E-05 | None | 0 | 0 | None | 0 | 1.64366E-04 | 4.7459E-05 | 0 | 4.80138E-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 | 0.9104 | likely_pathogenic | 0.8873 | pathogenic | -1.28 | Destabilizing | 0.999 | D | 0.655 | neutral | None | None | None | None | N |
| R/C | 0.4656 | ambiguous | 0.4365 | ambiguous | -1.354 | Destabilizing | 1.0 | D | 0.814 | deleterious | None | None | None | None | N |
| R/D | 0.9831 | likely_pathogenic | 0.979 | pathogenic | -0.5 | Destabilizing | 1.0 | D | 0.77 | deleterious | None | None | None | None | N |
| R/E | 0.8736 | likely_pathogenic | 0.8442 | pathogenic | -0.315 | Destabilizing | 0.999 | D | 0.642 | neutral | None | None | None | None | N |
| R/F | 0.9046 | likely_pathogenic | 0.8784 | pathogenic | -0.726 | Destabilizing | 1.0 | D | 0.807 | deleterious | None | None | None | None | N |
| R/G | 0.8853 | likely_pathogenic | 0.8715 | pathogenic | -1.649 | Destabilizing | 1.0 | D | 0.732 | prob.delet. | D | 0.546978219 | None | None | N |
| R/H | 0.3363 | likely_benign | 0.3063 | benign | -1.684 | Destabilizing | 1.0 | D | 0.747 | deleterious | None | None | None | None | N |
| R/I | 0.6494 | likely_pathogenic | 0.5948 | pathogenic | -0.248 | Destabilizing | 1.0 | D | 0.799 | deleterious | None | None | None | None | N |
| R/K | 0.2873 | likely_benign | 0.2477 | benign | -1.254 | Destabilizing | 0.998 | D | 0.543 | neutral | None | None | None | None | N |
| R/L | 0.6813 | likely_pathogenic | 0.6447 | pathogenic | -0.248 | Destabilizing | 1.0 | D | 0.732 | prob.delet. | D | 0.537860376 | None | None | N |
| R/M | 0.7051 | likely_pathogenic | 0.6551 | pathogenic | -0.688 | Destabilizing | 1.0 | D | 0.772 | deleterious | None | None | None | None | N |
| R/N | 0.9516 | likely_pathogenic | 0.9366 | pathogenic | -0.959 | Destabilizing | 1.0 | D | 0.737 | prob.delet. | None | None | None | None | N |
| R/P | 0.996 | likely_pathogenic | 0.9952 | pathogenic | -0.574 | Destabilizing | 1.0 | D | 0.765 | deleterious | D | 0.654538378 | None | None | N |
| R/Q | 0.3075 | likely_benign | 0.2777 | benign | -0.931 | Destabilizing | 1.0 | D | 0.733 | prob.delet. | N | 0.507422302 | None | None | N |
| R/S | 0.9326 | likely_pathogenic | 0.9156 | pathogenic | -1.777 | Destabilizing | 1.0 | D | 0.751 | deleterious | None | None | None | None | N |
| R/T | 0.7927 | likely_pathogenic | 0.7381 | pathogenic | -1.381 | Destabilizing | 1.0 | D | 0.741 | deleterious | None | None | None | None | N |
| R/V | 0.737 | likely_pathogenic | 0.6842 | pathogenic | -0.574 | Destabilizing | 1.0 | D | 0.792 | deleterious | None | None | None | None | N |
| R/W | 0.5109 | ambiguous | 0.4866 | ambiguous | -0.282 | Destabilizing | 1.0 | D | 0.807 | deleterious | None | None | None | None | N |
| R/Y | 0.7424 | likely_pathogenic | 0.7041 | pathogenic | -0.044 | Destabilizing | 1.0 | D | 0.793 | deleterious | 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.