Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24288 | 73087;73088;73089 | chr2:178573270;178573269;178573268 | chr2:179437997;179437996;179437995 |
| N2AB | 22647 | 68164;68165;68166 | chr2:178573270;178573269;178573268 | chr2:179437997;179437996;179437995 |
| N2A | 21720 | 65383;65384;65385 | chr2:178573270;178573269;178573268 | chr2:179437997;179437996;179437995 |
| N2B | 15223 | 45892;45893;45894 | chr2:178573270;178573269;178573268 | chr2:179437997;179437996;179437995 |
| Novex-1 | 15348 | 46267;46268;46269 | chr2:178573270;178573269;178573268 | chr2:179437997;179437996;179437995 |
| Novex-2 | 15415 | 46468;46469;46470 | chr2:178573270;178573269;178573268 | chr2:179437997;179437996;179437995 |
| 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 | None | None | 0.958 | N | 0.36 | 0.175 | 0.191931220699 | gnomAD-4.0.0 | 1.61366E-06 | None | None | None | None | N | None | 5.73526E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| T/R | rs878997916  |
None | 0.994 | N | 0.668 | 0.406 | 0.482061804652 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 2.88351E-04 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| T/R | rs878997916 |
None | 0.994 | N | 0.668 | 0.406 | 0.482061804652 | gnomAD-4.0.0 | 1.86923E-06 | None | None | None | None | N | None | 0 | 0 | None | 3.431E-05 | 0 | None | 0 | 0 | 1.7021E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.0969 | likely_benign | 0.089 | benign | -0.929 | Destabilizing | 0.958 | D | 0.36 | neutral | N | 0.503781495 | None | None | N |
| T/C | 0.4101 | ambiguous | 0.4164 | ambiguous | -0.465 | Destabilizing | 1.0 | D | 0.65 | neutral | None | None | None | None | N |
| T/D | 0.6401 | likely_pathogenic | 0.6059 | pathogenic | -0.09 | Destabilizing | 0.998 | D | 0.663 | neutral | None | None | None | None | N |
| T/E | 0.4517 | ambiguous | 0.434 | ambiguous | -0.084 | Destabilizing | 0.995 | D | 0.597 | neutral | None | None | None | None | N |
| T/F | 0.2535 | likely_benign | 0.2581 | benign | -0.959 | Destabilizing | 0.982 | D | 0.672 | neutral | None | None | None | None | N |
| T/G | 0.2987 | likely_benign | 0.2744 | benign | -1.194 | Destabilizing | 0.995 | D | 0.572 | neutral | None | None | None | None | N |
| T/H | 0.3009 | likely_benign | 0.3 | benign | -1.343 | Destabilizing | 0.998 | D | 0.679 | prob.neutral | None | None | None | None | N |
| T/I | 0.1198 | likely_benign | 0.1289 | benign | -0.309 | Destabilizing | 0.988 | D | 0.659 | neutral | N | 0.425822144 | None | None | N |
| T/K | 0.295 | likely_benign | 0.2834 | benign | -0.711 | Destabilizing | 0.994 | D | 0.615 | neutral | N | 0.461740085 | None | None | N |
| T/L | 0.0724 | likely_benign | 0.0732 | benign | -0.309 | Destabilizing | 0.938 | D | 0.478 | neutral | None | None | None | None | N |
| T/M | 0.0763 | likely_benign | 0.0754 | benign | -0.034 | Destabilizing | 1.0 | D | 0.665 | neutral | None | None | None | None | N |
| T/N | 0.1615 | likely_benign | 0.1459 | benign | -0.622 | Destabilizing | 0.995 | D | 0.649 | neutral | None | None | None | None | N |
| T/P | 0.2802 | likely_benign | 0.2231 | benign | -0.484 | Destabilizing | 0.998 | D | 0.667 | neutral | N | 0.474624468 | None | None | N |
| T/Q | 0.2494 | likely_benign | 0.2467 | benign | -0.761 | Destabilizing | 0.995 | D | 0.684 | prob.neutral | None | None | None | None | N |
| T/R | 0.2484 | likely_benign | 0.2405 | benign | -0.447 | Destabilizing | 0.994 | D | 0.668 | neutral | N | 0.470263567 | None | None | N |
| T/S | 0.1331 | likely_benign | 0.1202 | benign | -0.948 | Destabilizing | 0.979 | D | 0.387 | neutral | N | 0.467956768 | None | None | N |
| T/V | 0.0985 | likely_benign | 0.1053 | benign | -0.484 | Destabilizing | 0.968 | D | 0.448 | neutral | None | None | None | None | N |
| T/W | 0.5864 | likely_pathogenic | 0.5985 | pathogenic | -0.876 | Destabilizing | 0.999 | D | 0.663 | neutral | None | None | None | None | N |
| T/Y | 0.3202 | likely_benign | 0.3297 | benign | -0.664 | Destabilizing | 0.18 | N | 0.309 | 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.