Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 9425 | 28498;28499;28500 | chr2:178710824;178710823;178710822 | chr2:179575551;179575550;179575549 |
| N2AB | 9108 | 27547;27548;27549 | chr2:178710824;178710823;178710822 | chr2:179575551;179575550;179575549 |
| N2A | 8181 | 24766;24767;24768 | chr2:178710824;178710823;178710822 | chr2:179575551;179575550;179575549 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/L | rs755720364  |
0.051 | 1.0 | None | 0.659 | 0.399 | 0.759093710221 | gnomAD-2.1.1 | 8.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 5.57E-05 | None | 0 | None | 0 | 8.87E-06 | 0 |
| P/L | rs755720364 |
0.051 | 1.0 | None | 0.659 | 0.399 | 0.759093710221 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| P/L | rs755720364 |
0.051 | 1.0 | None | 0.659 | 0.399 | 0.759093710221 | gnomAD-4.0.0 | 4.33788E-06 | None | None | None | None | I | None | 0 | 1.66739E-05 | None | 0 | 0 | None | 0 | 0 | 5.0855E-06 | 0 | 0 |
| P/R | rs755720364 |
0.36 | 1.0 | None | 0.673 | 0.432 | 0.630366330378 | gnomAD-2.1.1 | 8.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.77E-05 | 0 |
| P/R | rs755720364 |
0.36 | 1.0 | None | 0.673 | 0.432 | 0.630366330378 | gnomAD-4.0.0 | 1.36832E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79885E-06 | 0 | 0 |
| P/S | None | None | 0.998 | None | 0.626 | 0.408 | 0.395143324098 | gnomAD-4.0.0 | 1.59102E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85785E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.2999 | likely_benign | 0.4111 | ambiguous | -0.506 | Destabilizing | 0.996 | D | 0.61 | neutral | None | None | None | None | I |
| P/C | 0.9296 | likely_pathogenic | 0.9677 | pathogenic | -0.551 | Destabilizing | 1.0 | D | 0.685 | prob.neutral | None | None | None | None | I |
| P/D | 0.6801 | likely_pathogenic | 0.7895 | pathogenic | -0.558 | Destabilizing | 1.0 | D | 0.653 | neutral | None | None | None | None | I |
| P/E | 0.6197 | likely_pathogenic | 0.7292 | pathogenic | -0.687 | Destabilizing | 1.0 | D | 0.648 | neutral | None | None | None | None | I |
| P/F | 0.8656 | likely_pathogenic | 0.941 | pathogenic | -0.811 | Destabilizing | 1.0 | D | 0.677 | prob.neutral | None | None | None | None | I |
| P/G | 0.6295 | likely_pathogenic | 0.7598 | pathogenic | -0.622 | Destabilizing | 1.0 | D | 0.621 | neutral | None | None | None | None | I |
| P/H | 0.5756 | likely_pathogenic | 0.7373 | pathogenic | -0.246 | Destabilizing | 1.0 | D | 0.655 | neutral | None | None | None | None | I |
| P/I | 0.7241 | likely_pathogenic | 0.869 | pathogenic | -0.353 | Destabilizing | 0.999 | D | 0.684 | prob.neutral | None | None | None | None | I |
| P/K | 0.7006 | likely_pathogenic | 0.8472 | pathogenic | -0.519 | Destabilizing | 1.0 | D | 0.65 | neutral | None | None | None | None | I |
| P/L | 0.4254 | ambiguous | 0.5791 | pathogenic | -0.353 | Destabilizing | 1.0 | D | 0.659 | neutral | None | None | None | None | I |
| P/M | 0.693 | likely_pathogenic | 0.8354 | pathogenic | -0.353 | Destabilizing | 1.0 | D | 0.652 | neutral | None | None | None | None | I |
| P/N | 0.5854 | likely_pathogenic | 0.7284 | pathogenic | -0.188 | Destabilizing | 1.0 | D | 0.654 | neutral | None | None | None | None | I |
| P/Q | 0.5118 | ambiguous | 0.6591 | pathogenic | -0.478 | Destabilizing | 1.0 | D | 0.634 | neutral | None | None | None | None | I |
| P/R | 0.559 | ambiguous | 0.7184 | pathogenic | 0.049 | Stabilizing | 1.0 | D | 0.673 | neutral | None | None | None | None | I |
| P/S | 0.428 | ambiguous | 0.574 | pathogenic | -0.483 | Destabilizing | 0.998 | D | 0.626 | neutral | None | None | None | None | I |
| P/T | 0.3552 | ambiguous | 0.5229 | ambiguous | -0.522 | Destabilizing | 0.884 | D | 0.443 | neutral | None | None | None | None | I |
| P/V | 0.5701 | likely_pathogenic | 0.7501 | pathogenic | -0.37 | Destabilizing | 0.999 | D | 0.622 | neutral | None | None | None | None | I |
| P/W | 0.9287 | likely_pathogenic | 0.9715 | pathogenic | -0.883 | Destabilizing | 1.0 | D | 0.701 | prob.neutral | None | None | None | None | I |
| P/Y | 0.805 | likely_pathogenic | 0.9086 | pathogenic | -0.592 | Destabilizing | 1.0 | D | 0.675 | prob.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.