Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28766 | 86521;86522;86523 | chr2:178559836;178559835;178559834 | chr2:179424563;179424562;179424561 |
| N2AB | 27125 | 81598;81599;81600 | chr2:178559836;178559835;178559834 | chr2:179424563;179424562;179424561 |
| N2A | 26198 | 78817;78818;78819 | chr2:178559836;178559835;178559834 | chr2:179424563;179424562;179424561 |
| N2B | 19701 | 59326;59327;59328 | chr2:178559836;178559835;178559834 | chr2:179424563;179424562;179424561 |
| Novex-1 | 19826 | 59701;59702;59703 | chr2:178559836;178559835;178559834 | chr2:179424563;179424562;179424561 |
| Novex-2 | 19893 | 59902;59903;59904 | chr2:178559836;178559835;178559834 | chr2:179424563;179424562;179424561 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | rs754113086  |
-1.311 | 0.999 | N | 0.489 | 0.681 | 0.735764439114 | gnomAD-2.1.1 | 4.05E-06 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| V/A | rs754113086 |
-1.311 | 0.999 | N | 0.489 | 0.681 | 0.735764439114 | gnomAD-4.0.0 | 6.85577E-07 | None | None | None | None | N | None | 0 | 2.23794E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/G | None | None | 1.0 | D | 0.695 | 0.816 | 0.935219820968 | gnomAD-4.0.0 | 6.85577E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99572E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.6491 | likely_pathogenic | 0.6406 | pathogenic | -1.704 | Destabilizing | 0.999 | D | 0.489 | neutral | N | 0.496776508 | None | None | N |
| V/C | 0.8791 | likely_pathogenic | 0.8801 | pathogenic | -1.206 | Destabilizing | 1.0 | D | 0.635 | neutral | None | None | None | None | N |
| V/D | 0.9888 | likely_pathogenic | 0.9873 | pathogenic | -1.982 | Destabilizing | 1.0 | D | 0.708 | prob.delet. | D | 0.541030549 | None | None | N |
| V/E | 0.9506 | likely_pathogenic | 0.9442 | pathogenic | -1.787 | Destabilizing | 1.0 | D | 0.683 | prob.neutral | None | None | None | None | N |
| V/F | 0.6515 | likely_pathogenic | 0.6226 | pathogenic | -0.982 | Destabilizing | 1.0 | D | 0.731 | prob.delet. | D | 0.540270081 | None | None | N |
| V/G | 0.8278 | likely_pathogenic | 0.8207 | pathogenic | -2.221 | Highly Destabilizing | 1.0 | D | 0.695 | prob.neutral | D | 0.551879876 | None | None | N |
| V/H | 0.9785 | likely_pathogenic | 0.9763 | pathogenic | -1.983 | Destabilizing | 1.0 | D | 0.639 | neutral | None | None | None | None | N |
| V/I | 0.0991 | likely_benign | 0.0928 | benign | -0.29 | Destabilizing | 0.997 | D | 0.509 | neutral | N | 0.491611948 | None | None | N |
| V/K | 0.9414 | likely_pathogenic | 0.9362 | pathogenic | -1.446 | Destabilizing | 1.0 | D | 0.68 | prob.neutral | None | None | None | None | N |
| V/L | 0.5153 | ambiguous | 0.4578 | ambiguous | -0.29 | Destabilizing | 0.997 | D | 0.513 | neutral | N | 0.504653774 | None | None | N |
| V/M | 0.4837 | ambiguous | 0.45 | ambiguous | -0.31 | Destabilizing | 1.0 | D | 0.745 | deleterious | None | None | None | None | N |
| V/N | 0.9572 | likely_pathogenic | 0.9532 | pathogenic | -1.685 | Destabilizing | 1.0 | D | 0.698 | prob.neutral | None | None | None | None | N |
| V/P | 0.9906 | likely_pathogenic | 0.9898 | pathogenic | -0.731 | Destabilizing | 1.0 | D | 0.686 | prob.neutral | None | None | None | None | N |
| V/Q | 0.9142 | likely_pathogenic | 0.9095 | pathogenic | -1.542 | Destabilizing | 1.0 | D | 0.676 | prob.neutral | None | None | None | None | N |
| V/R | 0.913 | likely_pathogenic | 0.9079 | pathogenic | -1.303 | Destabilizing | 1.0 | D | 0.692 | prob.neutral | None | None | None | None | N |
| V/S | 0.8461 | likely_pathogenic | 0.8434 | pathogenic | -2.315 | Highly Destabilizing | 1.0 | D | 0.683 | prob.neutral | None | None | None | None | N |
| V/T | 0.6678 | likely_pathogenic | 0.6669 | pathogenic | -1.973 | Destabilizing | 0.999 | D | 0.652 | neutral | None | None | None | None | N |
| V/W | 0.9893 | likely_pathogenic | 0.9882 | pathogenic | -1.481 | Destabilizing | 1.0 | D | 0.619 | neutral | None | None | None | None | N |
| V/Y | 0.9551 | likely_pathogenic | 0.9499 | pathogenic | -1.044 | Destabilizing | 1.0 | D | 0.728 | 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.