Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30398 | 91417;91418;91419 | chr2:178551708;178551707;178551706 | chr2:179416435;179416434;179416433 |
| N2AB | 28757 | 86494;86495;86496 | chr2:178551708;178551707;178551706 | chr2:179416435;179416434;179416433 |
| N2A | 27830 | 83713;83714;83715 | chr2:178551708;178551707;178551706 | chr2:179416435;179416434;179416433 |
| N2B | 21333 | 64222;64223;64224 | chr2:178551708;178551707;178551706 | chr2:179416435;179416434;179416433 |
| Novex-1 | 21458 | 64597;64598;64599 | chr2:178551708;178551707;178551706 | chr2:179416435;179416434;179416433 |
| Novex-2 | 21525 | 64798;64799;64800 | chr2:178551708;178551707;178551706 | chr2:179416435;179416434;179416433 |
| 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/C | rs765097933  |
-1.64 | 1.0 | D | 0.72 | 0.539 | 0.83723574227 | gnomAD-2.1.1 | 2.14E-05 | None | None | None | None | N | None | 4.13E-05 | 0 | None | 0 | 5.13E-05 | None | 3.27E-05 | None | 0 | 2.35E-05 | 0 |
| R/C | rs765097933 |
-1.64 | 1.0 | D | 0.72 | 0.539 | 0.83723574227 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| R/C | rs765097933 |
-1.64 | 1.0 | D | 0.72 | 0.539 | 0.83723574227 | gnomAD-4.0.0 | 9.29732E-06 | None | None | None | None | N | None | 1.33522E-05 | 0 | None | 0 | 2.22836E-05 | None | 0 | 0 | 7.62943E-06 | 2.19708E-05 | 3.20318E-05 |
| R/H | rs761570672 |
-2.649 | 0.998 | D | 0.61 | 0.514 | 0.504052602331 | gnomAD-2.1.1 | 1.79E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 6.54E-05 | None | 4.01E-05 | 1.56E-05 | 0 |
| R/H | rs761570672 |
-2.649 | 0.998 | D | 0.61 | 0.514 | 0.504052602331 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 9.42E-05 | 0 | 2.94E-05 | 0 | 0 |
| R/H | rs761570672 |
-2.649 | 0.998 | D | 0.61 | 0.514 | 0.504052602331 | gnomAD-4.0.0 | 1.23963E-05 | None | None | None | None | N | None | 1.33515E-05 | 0 | None | 0 | 0 | None | 1.56274E-05 | 0 | 1.18682E-05 | 2.19674E-05 | 3.20297E-05 |
| R/S | None | None | 0.975 | N | 0.599 | 0.498 | 0.632750256606 | gnomAD-4.0.0 | 6.84361E-07 | None | None | None | None | N | None | 2.99079E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 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 | 0.9668 | likely_pathogenic | 0.9791 | pathogenic | -2.263 | Highly Destabilizing | 0.953 | D | 0.603 | neutral | None | None | None | None | N |
| R/C | 0.4956 | ambiguous | 0.6172 | pathogenic | -1.9 | Destabilizing | 1.0 | D | 0.72 | prob.delet. | D | 0.528068768 | None | None | N |
| R/D | 0.9975 | likely_pathogenic | 0.9986 | pathogenic | -1.413 | Destabilizing | 0.986 | D | 0.629 | neutral | None | None | None | None | N |
| R/E | 0.9617 | likely_pathogenic | 0.9757 | pathogenic | -1.189 | Destabilizing | 0.91 | D | 0.613 | neutral | None | None | None | None | N |
| R/F | 0.9744 | likely_pathogenic | 0.9851 | pathogenic | -1.301 | Destabilizing | 0.998 | D | 0.739 | prob.delet. | None | None | None | None | N |
| R/G | 0.9663 | likely_pathogenic | 0.9807 | pathogenic | -2.565 | Highly Destabilizing | 0.975 | D | 0.609 | neutral | D | 0.55052789 | None | None | N |
| R/H | 0.4057 | ambiguous | 0.523 | ambiguous | -2.35 | Highly Destabilizing | 0.998 | D | 0.61 | neutral | D | 0.528068768 | None | None | N |
| R/I | 0.9116 | likely_pathogenic | 0.9368 | pathogenic | -1.357 | Destabilizing | 0.993 | D | 0.725 | prob.delet. | None | None | None | None | N |
| R/K | 0.3648 | ambiguous | 0.4414 | ambiguous | -1.261 | Destabilizing | 0.807 | D | 0.653 | neutral | None | None | None | None | N |
| R/L | 0.8542 | likely_pathogenic | 0.8931 | pathogenic | -1.357 | Destabilizing | 0.975 | D | 0.609 | neutral | N | 0.506179078 | None | None | N |
| R/M | 0.9141 | likely_pathogenic | 0.9463 | pathogenic | -1.853 | Destabilizing | 0.998 | D | 0.65 | neutral | None | None | None | None | N |
| R/N | 0.9885 | likely_pathogenic | 0.9934 | pathogenic | -1.522 | Destabilizing | 0.986 | D | 0.559 | neutral | None | None | None | None | N |
| R/P | 0.9988 | likely_pathogenic | 0.9991 | pathogenic | -1.654 | Destabilizing | 0.996 | D | 0.679 | prob.neutral | D | 0.551034869 | None | None | N |
| R/Q | 0.3777 | ambiguous | 0.4824 | ambiguous | -1.255 | Destabilizing | 0.386 | N | 0.416 | neutral | None | None | None | None | N |
| R/S | 0.978 | likely_pathogenic | 0.9875 | pathogenic | -2.251 | Highly Destabilizing | 0.975 | D | 0.599 | neutral | N | 0.515303203 | None | None | N |
| R/T | 0.9595 | likely_pathogenic | 0.9762 | pathogenic | -1.834 | Destabilizing | 0.986 | D | 0.591 | neutral | None | None | None | None | N |
| R/V | 0.9241 | likely_pathogenic | 0.946 | pathogenic | -1.654 | Destabilizing | 0.993 | D | 0.699 | prob.neutral | None | None | None | None | N |
| R/W | 0.7813 | likely_pathogenic | 0.858 | pathogenic | -0.911 | Destabilizing | 0.999 | D | 0.687 | prob.neutral | None | None | None | None | N |
| R/Y | 0.9321 | likely_pathogenic | 0.9603 | pathogenic | -0.871 | Destabilizing | 0.998 | D | 0.704 | 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.