Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21227 | 63904;63905;63906 | chr2:178587630;178587629;178587628 | chr2:179452357;179452356;179452355 |
| N2AB | 19586 | 58981;58982;58983 | chr2:178587630;178587629;178587628 | chr2:179452357;179452356;179452355 |
| N2A | 18659 | 56200;56201;56202 | chr2:178587630;178587629;178587628 | chr2:179452357;179452356;179452355 |
| N2B | 12162 | 36709;36710;36711 | chr2:178587630;178587629;178587628 | chr2:179452357;179452356;179452355 |
| Novex-1 | 12287 | 37084;37085;37086 | chr2:178587630;178587629;178587628 | chr2:179452357;179452356;179452355 |
| Novex-2 | 12354 | 37285;37286;37287 | chr2:178587630;178587629;178587628 | chr2:179452357;179452356;179452355 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | rs752958666  |
-0.327 | 0.999 | N | 0.586 | 0.442 | None | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.92E-06 | 0 |
| T/A | rs752958666 |
-0.327 | 0.999 | N | 0.586 | 0.442 | None | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 2.42E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| T/A | rs752958666 |
-0.327 | 0.999 | N | 0.586 | 0.442 | None | gnomAD-4.0.0 | 4.34069E-06 | None | None | None | None | N | None | 1.33629E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 3.39152E-06 | 0 | 3.20482E-05 |
| T/P | None | None | 1.0 | N | 0.702 | 0.521 | 0.633985563651 | gnomAD-4.0.0 | 6.84621E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99722E-07 | 0 | 0 |
| T/S | rs752958666 |
None | 0.999 | N | 0.619 | 0.36 | 0.472741223727 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| T/S | rs752958666 |
None | 0.999 | N | 0.619 | 0.36 | 0.472741223727 | gnomAD-4.0.0 | 6.57964E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.4715E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.179 | likely_benign | 0.1533 | benign | -0.553 | Destabilizing | 0.999 | D | 0.586 | neutral | N | 0.517375229 | None | None | N |
| T/C | 0.6756 | likely_pathogenic | 0.6422 | pathogenic | -0.324 | Destabilizing | 1.0 | D | 0.626 | neutral | None | None | None | None | N |
| T/D | 0.5193 | ambiguous | 0.4425 | ambiguous | 0.051 | Stabilizing | 1.0 | D | 0.737 | prob.delet. | None | None | None | None | N |
| T/E | 0.5677 | likely_pathogenic | 0.5014 | ambiguous | 0.04 | Stabilizing | 1.0 | D | 0.736 | prob.delet. | None | None | None | None | N |
| T/F | 0.6945 | likely_pathogenic | 0.6449 | pathogenic | -0.649 | Destabilizing | 1.0 | D | 0.721 | prob.delet. | None | None | None | None | N |
| T/G | 0.3169 | likely_benign | 0.2768 | benign | -0.793 | Destabilizing | 1.0 | D | 0.719 | prob.delet. | None | None | None | None | N |
| T/H | 0.4543 | ambiguous | 0.376 | ambiguous | -1.038 | Destabilizing | 1.0 | D | 0.675 | prob.neutral | None | None | None | None | N |
| T/I | 0.7132 | likely_pathogenic | 0.6746 | pathogenic | -0.012 | Destabilizing | 1.0 | D | 0.716 | prob.delet. | N | 0.4954297 | None | None | N |
| T/K | 0.4311 | ambiguous | 0.3648 | ambiguous | -0.648 | Destabilizing | 1.0 | D | 0.738 | prob.delet. | None | None | None | None | N |
| T/L | 0.3631 | ambiguous | 0.3293 | benign | -0.012 | Destabilizing | 0.999 | D | 0.672 | neutral | None | None | None | None | N |
| T/M | 0.2246 | likely_benign | 0.198 | benign | 0.067 | Stabilizing | 1.0 | D | 0.633 | neutral | None | None | None | None | N |
| T/N | 0.182 | likely_benign | 0.1479 | benign | -0.496 | Destabilizing | 1.0 | D | 0.712 | prob.delet. | N | 0.479376988 | None | None | N |
| T/P | 0.4034 | ambiguous | 0.3379 | benign | -0.16 | Destabilizing | 1.0 | D | 0.702 | prob.neutral | N | 0.484073395 | None | None | N |
| T/Q | 0.4093 | ambiguous | 0.3465 | ambiguous | -0.606 | Destabilizing | 1.0 | D | 0.694 | prob.neutral | None | None | None | None | N |
| T/R | 0.3866 | ambiguous | 0.3203 | benign | -0.438 | Destabilizing | 1.0 | D | 0.7 | prob.neutral | None | None | None | None | N |
| T/S | 0.1555 | likely_benign | 0.1319 | benign | -0.741 | Destabilizing | 0.999 | D | 0.619 | neutral | N | 0.410055763 | None | None | N |
| T/V | 0.5182 | ambiguous | 0.4851 | ambiguous | -0.16 | Destabilizing | 0.999 | D | 0.658 | neutral | None | None | None | None | N |
| T/W | 0.8918 | likely_pathogenic | 0.8683 | pathogenic | -0.656 | Destabilizing | 1.0 | D | 0.667 | neutral | None | None | None | None | N |
| T/Y | 0.6213 | likely_pathogenic | 0.5697 | pathogenic | -0.412 | Destabilizing | 1.0 | D | 0.715 | 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.