Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27155 | 81688;81689;81690 | chr2:178564669;178564668;178564667 | chr2:179429396;179429395;179429394 |
| N2AB | 25514 | 76765;76766;76767 | chr2:178564669;178564668;178564667 | chr2:179429396;179429395;179429394 |
| N2A | 24587 | 73984;73985;73986 | chr2:178564669;178564668;178564667 | chr2:179429396;179429395;179429394 |
| N2B | 18090 | 54493;54494;54495 | chr2:178564669;178564668;178564667 | chr2:179429396;179429395;179429394 |
| Novex-1 | 18215 | 54868;54869;54870 | chr2:178564669;178564668;178564667 | chr2:179429396;179429395;179429394 |
| Novex-2 | 18282 | 55069;55070;55071 | chr2:178564669;178564668;178564667 | chr2:179429396;179429395;179429394 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/T | rs397517720  |
-0.877 | 0.549 | N | 0.519 | 0.277 | None | gnomAD-2.1.1 | 7.15E-05 | None | None | None | None | I | None | 2.48077E-04 | 2.84E-05 | None | 0 | 0 | None | 1.96168E-04 | None | 0 | 5.48E-05 | 0 |
| I/T | rs397517720 |
-0.877 | 0.549 | N | 0.519 | 0.277 | None | gnomAD-3.1.2 | 1.11739E-04 | None | None | None | None | I | None | 4.10093E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/T | rs397517720 |
-0.877 | 0.549 | N | 0.519 | 0.277 | None | gnomAD-4.0.0 | 4.46255E-05 | None | None | None | None | I | None | 4.4054E-04 | 1.66817E-05 | None | 0 | 2.23384E-05 | None | 0 | 0 | 2.03439E-05 | 9.88207E-05 | 6.40636E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.1614 | likely_benign | 0.1394 | benign | -1.161 | Destabilizing | 0.25 | N | 0.505 | neutral | None | None | None | None | I |
| I/C | 0.5224 | ambiguous | 0.4824 | ambiguous | -0.641 | Destabilizing | 0.977 | D | 0.581 | neutral | None | None | None | None | I |
| I/D | 0.7467 | likely_pathogenic | 0.6867 | pathogenic | -0.675 | Destabilizing | 0.972 | D | 0.673 | neutral | None | None | None | None | I |
| I/E | 0.552 | ambiguous | 0.4922 | ambiguous | -0.757 | Destabilizing | 0.92 | D | 0.666 | neutral | None | None | None | None | I |
| I/F | 0.1685 | likely_benign | 0.1525 | benign | -1.094 | Destabilizing | 0.81 | D | 0.586 | neutral | N | 0.461601733 | None | None | I |
| I/G | 0.5694 | likely_pathogenic | 0.5198 | ambiguous | -1.381 | Destabilizing | 0.92 | D | 0.661 | neutral | None | None | None | None | I |
| I/H | 0.5104 | ambiguous | 0.4482 | ambiguous | -0.574 | Destabilizing | 0.992 | D | 0.659 | neutral | None | None | None | None | I |
| I/K | 0.2899 | likely_benign | 0.2442 | benign | -0.552 | Destabilizing | 0.92 | D | 0.663 | neutral | None | None | None | None | I |
| I/L | 0.1248 | likely_benign | 0.1139 | benign | -0.679 | Destabilizing | 0.001 | N | 0.208 | neutral | N | 0.446671845 | None | None | I |
| I/M | 0.1053 | likely_benign | 0.099 | benign | -0.419 | Destabilizing | 0.81 | D | 0.623 | neutral | N | 0.508664453 | None | None | I |
| I/N | 0.3349 | likely_benign | 0.2828 | benign | -0.259 | Destabilizing | 0.963 | D | 0.67 | neutral | N | 0.518553373 | None | None | I |
| I/P | 0.4356 | ambiguous | 0.3984 | ambiguous | -0.806 | Destabilizing | 0.972 | D | 0.671 | neutral | None | None | None | None | I |
| I/Q | 0.3928 | ambiguous | 0.3442 | ambiguous | -0.566 | Destabilizing | 0.972 | D | 0.669 | neutral | None | None | None | None | I |
| I/R | 0.2253 | likely_benign | 0.1898 | benign | 0.118 | Stabilizing | 0.92 | D | 0.671 | neutral | None | None | None | None | I |
| I/S | 0.2525 | likely_benign | 0.2116 | benign | -0.782 | Destabilizing | 0.81 | D | 0.651 | neutral | N | 0.507797661 | None | None | I |
| I/T | 0.0846 | likely_benign | 0.0755 | benign | -0.755 | Destabilizing | 0.549 | D | 0.519 | neutral | N | 0.47510924 | None | None | I |
| I/V | 0.0615 | likely_benign | 0.0608 | benign | -0.806 | Destabilizing | 0.002 | N | 0.213 | neutral | N | 0.442266103 | None | None | I |
| I/W | 0.7375 | likely_pathogenic | 0.7063 | pathogenic | -1.063 | Destabilizing | 0.992 | D | 0.685 | prob.neutral | None | None | None | None | I |
| I/Y | 0.535 | ambiguous | 0.5057 | ambiguous | -0.827 | Destabilizing | 0.92 | D | 0.615 | neutral | None | None | None | None | I |
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.