Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 33107 | 99544;99545;99546 | chr2:178537888;178537887;178537886 | chr2:179402615;179402614;179402613 |
| N2AB | 31466 | 94621;94622;94623 | chr2:178537888;178537887;178537886 | chr2:179402615;179402614;179402613 |
| N2A | 30539 | 91840;91841;91842 | chr2:178537888;178537887;178537886 | chr2:179402615;179402614;179402613 |
| N2B | 24042 | 72349;72350;72351 | chr2:178537888;178537887;178537886 | chr2:179402615;179402614;179402613 |
| Novex-1 | 24167 | 72724;72725;72726 | chr2:178537888;178537887;178537886 | chr2:179402615;179402614;179402613 |
| Novex-2 | 24234 | 72925;72926;72927 | chr2:178537888;178537887;178537886 | chr2:179402615;179402614;179402613 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/I | None | None | 0.001 | N | 0.093 | 0.116 | 0.239901079897 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| M/T | rs942438397  |
None | 0.512 | N | 0.537 | 0.419 | 0.642270024921 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 4.78011E-04 |
| M/T | rs942438397 |
None | 0.512 | N | 0.537 | 0.419 | 0.642270024921 | gnomAD-4.0.0 | 5.07487E-06 | None | None | None | None | N | None | 6.99105E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.40252E-05 |
| M/V | None | None | 0.121 | N | 0.324 | 0.094 | 0.234412748748 | gnomAD-4.0.0 | 2.73991E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.6012E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.8322 | likely_pathogenic | 0.8475 | pathogenic | -1.333 | Destabilizing | 0.823 | D | 0.487 | neutral | None | None | None | None | N |
| M/C | 0.933 | likely_pathogenic | 0.9348 | pathogenic | -1.442 | Destabilizing | 0.996 | D | 0.655 | neutral | None | None | None | None | N |
| M/D | 0.9954 | likely_pathogenic | 0.9951 | pathogenic | -0.585 | Destabilizing | 1.0 | D | 0.705 | prob.neutral | None | None | None | None | N |
| M/E | 0.9739 | likely_pathogenic | 0.9739 | pathogenic | -0.556 | Destabilizing | 0.996 | D | 0.645 | neutral | None | None | None | None | N |
| M/F | 0.7696 | likely_pathogenic | 0.761 | pathogenic | -0.657 | Destabilizing | 0.344 | N | 0.522 | neutral | None | None | None | None | N |
| M/G | 0.9404 | likely_pathogenic | 0.9389 | pathogenic | -1.634 | Destabilizing | 1.0 | D | 0.637 | neutral | None | None | None | None | N |
| M/H | 0.9883 | likely_pathogenic | 0.9864 | pathogenic | -0.91 | Destabilizing | 0.99 | D | 0.64 | neutral | None | None | None | None | N |
| M/I | 0.3915 | ambiguous | 0.4478 | ambiguous | -0.569 | Destabilizing | 0.001 | N | 0.093 | neutral | N | 0.408857244 | None | None | N |
| M/K | 0.9511 | likely_pathogenic | 0.9421 | pathogenic | -0.204 | Destabilizing | 0.99 | D | 0.585 | neutral | N | 0.468078906 | None | None | N |
| M/L | 0.1765 | likely_benign | 0.1411 | benign | -0.569 | Destabilizing | 0.001 | N | 0.083 | neutral | N | 0.290123132 | None | None | N |
| M/N | 0.9539 | likely_pathogenic | 0.9575 | pathogenic | -0.148 | Destabilizing | 1.0 | D | 0.688 | prob.neutral | None | None | None | None | N |
| M/P | 0.9105 | likely_pathogenic | 0.908 | pathogenic | -0.796 | Destabilizing | 1.0 | D | 0.689 | prob.neutral | None | None | None | None | N |
| M/Q | 0.9051 | likely_pathogenic | 0.9019 | pathogenic | -0.248 | Destabilizing | 1.0 | D | 0.604 | neutral | None | None | None | None | N |
| M/R | 0.9556 | likely_pathogenic | 0.9456 | pathogenic | 0.093 | Stabilizing | 1.0 | D | 0.686 | prob.neutral | N | 0.454341605 | None | None | N |
| M/S | 0.9365 | likely_pathogenic | 0.9451 | pathogenic | -0.736 | Destabilizing | 0.999 | D | 0.567 | neutral | None | None | None | None | N |
| M/T | 0.8417 | likely_pathogenic | 0.8493 | pathogenic | -0.59 | Destabilizing | 0.512 | D | 0.537 | neutral | N | 0.426250926 | None | None | N |
| M/V | 0.2171 | likely_benign | 0.232 | benign | -0.796 | Destabilizing | 0.121 | N | 0.324 | neutral | N | 0.420517033 | None | None | N |
| M/W | 0.9808 | likely_pathogenic | 0.9759 | pathogenic | -0.653 | Destabilizing | 0.999 | D | 0.637 | neutral | None | None | None | None | N |
| M/Y | 0.9775 | likely_pathogenic | 0.9762 | pathogenic | -0.529 | Destabilizing | 0.993 | D | 0.686 | 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.