Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26197 | 78814;78815;78816 | chr2:178567543;178567542;178567541 | chr2:179432270;179432269;179432268 |
| N2AB | 24556 | 73891;73892;73893 | chr2:178567543;178567542;178567541 | chr2:179432270;179432269;179432268 |
| N2A | 23629 | 71110;71111;71112 | chr2:178567543;178567542;178567541 | chr2:179432270;179432269;179432268 |
| N2B | 17132 | 51619;51620;51621 | chr2:178567543;178567542;178567541 | chr2:179432270;179432269;179432268 |
| Novex-1 | 17257 | 51994;51995;51996 | chr2:178567543;178567542;178567541 | chr2:179432270;179432269;179432268 |
| Novex-2 | 17324 | 52195;52196;52197 | chr2:178567543;178567542;178567541 | chr2:179432270;179432269;179432268 |
| 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/A | rs747052899  |
None | 0.058 | N | 0.413 | 0.22 | 0.17258766438 | gnomAD-4.0.0 | 3.42842E-06 | None | None | None | None | N | None | 2.99724E-05 | 0 | None | 0 | 0 | None | 0 | 1.74095E-04 | 2.70176E-06 | 0 | 0 |
| P/T | rs747052899 |
-1.66 | 0.698 | N | 0.638 | 0.413 | 0.40528724903 | gnomAD-2.1.1 | 4.08E-06 | None | None | None | None | N | None | 6.48E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| P/T | rs747052899 |
-1.66 | 0.698 | N | 0.638 | 0.413 | 0.40528724903 | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| P/T | rs747052899 |
-1.66 | 0.698 | N | 0.638 | 0.413 | 0.40528724903 | gnomAD-4.0.0 | 5.58866E-06 | None | None | None | None | N | None | 6.68771E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 3.39452E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.1747 | likely_benign | 0.147 | benign | -0.687 | Destabilizing | 0.058 | N | 0.413 | neutral | N | 0.457630705 | None | None | N |
| P/C | 0.8187 | likely_pathogenic | 0.7519 | pathogenic | -0.694 | Destabilizing | 0.998 | D | 0.725 | prob.delet. | None | None | None | None | N |
| P/D | 0.8134 | likely_pathogenic | 0.7307 | pathogenic | -0.578 | Destabilizing | 0.956 | D | 0.686 | prob.neutral | None | None | None | None | N |
| P/E | 0.6036 | likely_pathogenic | 0.5169 | ambiguous | -0.668 | Destabilizing | 0.86 | D | 0.669 | neutral | None | None | None | None | N |
| P/F | 0.8047 | likely_pathogenic | 0.7495 | pathogenic | -0.767 | Destabilizing | 0.956 | D | 0.737 | prob.delet. | None | None | None | None | N |
| P/G | 0.612 | likely_pathogenic | 0.508 | ambiguous | -0.851 | Destabilizing | 0.86 | D | 0.646 | neutral | None | None | None | None | N |
| P/H | 0.5032 | ambiguous | 0.4276 | ambiguous | -0.309 | Destabilizing | 0.998 | D | 0.71 | prob.delet. | None | None | None | None | N |
| P/I | 0.5194 | ambiguous | 0.4629 | ambiguous | -0.388 | Destabilizing | 0.915 | D | 0.695 | prob.neutral | None | None | None | None | N |
| P/K | 0.6736 | likely_pathogenic | 0.5787 | pathogenic | -0.683 | Destabilizing | 0.86 | D | 0.662 | neutral | None | None | None | None | N |
| P/L | 0.2868 | likely_benign | 0.2822 | benign | -0.388 | Destabilizing | 0.014 | N | 0.561 | neutral | N | 0.517737801 | None | None | N |
| P/M | 0.5325 | ambiguous | 0.4658 | ambiguous | -0.469 | Destabilizing | 0.988 | D | 0.713 | prob.delet. | None | None | None | None | N |
| P/N | 0.6929 | likely_pathogenic | 0.6043 | pathogenic | -0.452 | Destabilizing | 0.956 | D | 0.685 | prob.neutral | None | None | None | None | N |
| P/Q | 0.402 | ambiguous | 0.3233 | benign | -0.682 | Destabilizing | 0.97 | D | 0.719 | prob.delet. | N | 0.484102032 | None | None | N |
| P/R | 0.508 | ambiguous | 0.4178 | ambiguous | -0.108 | Destabilizing | 0.97 | D | 0.719 | prob.delet. | N | 0.485740026 | None | None | N |
| P/S | 0.3029 | likely_benign | 0.2524 | benign | -0.808 | Destabilizing | 0.153 | N | 0.406 | neutral | N | 0.484374589 | None | None | N |
| P/T | 0.2314 | likely_benign | 0.2015 | benign | -0.797 | Destabilizing | 0.698 | D | 0.638 | neutral | N | 0.502713266 | None | None | N |
| P/V | 0.355 | ambiguous | 0.3066 | benign | -0.453 | Destabilizing | 0.754 | D | 0.665 | neutral | None | None | None | None | N |
| P/W | 0.8969 | likely_pathogenic | 0.8488 | pathogenic | -0.859 | Destabilizing | 0.998 | D | 0.731 | prob.delet. | None | None | None | None | N |
| P/Y | 0.7764 | likely_pathogenic | 0.7126 | pathogenic | -0.578 | Destabilizing | 0.978 | D | 0.739 | prob.delet. | 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.