Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27118 | 81577;81578;81579 | chr2:178564780;178564779;178564778 | chr2:179429507;179429506;179429505 |
| N2AB | 25477 | 76654;76655;76656 | chr2:178564780;178564779;178564778 | chr2:179429507;179429506;179429505 |
| N2A | 24550 | 73873;73874;73875 | chr2:178564780;178564779;178564778 | chr2:179429507;179429506;179429505 |
| N2B | 18053 | 54382;54383;54384 | chr2:178564780;178564779;178564778 | chr2:179429507;179429506;179429505 |
| Novex-1 | 18178 | 54757;54758;54759 | chr2:178564780;178564779;178564778 | chr2:179429507;179429506;179429505 |
| Novex-2 | 18245 | 54958;54959;54960 | chr2:178564780;178564779;178564778 | chr2:179429507;179429506;179429505 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/S | None | None | 1.0 | N | 0.671 | 0.49 | 0.763842213962 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| L/V | rs1293763784  |
-0.158 | 0.999 | N | 0.535 | 0.191 | 0.490839437361 | gnomAD-2.1.1 | 4.1E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 5.74E-05 | None | 0 | None | 0 | 0 | 0 |
| L/V | rs1293763784 |
-0.158 | 0.999 | N | 0.535 | 0.191 | 0.490839437361 | gnomAD-4.0.0 | 1.59518E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 2.78831E-05 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.8011 | likely_pathogenic | 0.783 | pathogenic | -0.715 | Destabilizing | 0.999 | D | 0.552 | neutral | None | None | None | None | I |
| L/C | 0.8558 | likely_pathogenic | 0.8517 | pathogenic | -0.712 | Destabilizing | 1.0 | D | 0.622 | neutral | None | None | None | None | I |
| L/D | 0.9829 | likely_pathogenic | 0.9792 | pathogenic | -0.201 | Destabilizing | 1.0 | D | 0.731 | prob.delet. | None | None | None | None | I |
| L/E | 0.921 | likely_pathogenic | 0.9033 | pathogenic | -0.253 | Destabilizing | 1.0 | D | 0.736 | prob.delet. | None | None | None | None | I |
| L/F | 0.4907 | ambiguous | 0.4723 | ambiguous | -0.582 | Destabilizing | 1.0 | D | 0.583 | neutral | N | 0.485371663 | None | None | I |
| L/G | 0.9331 | likely_pathogenic | 0.9296 | pathogenic | -0.893 | Destabilizing | 1.0 | D | 0.735 | prob.delet. | None | None | None | None | I |
| L/H | 0.7156 | likely_pathogenic | 0.6889 | pathogenic | 0.002 | Stabilizing | 1.0 | D | 0.733 | prob.delet. | None | None | None | None | I |
| L/I | 0.2117 | likely_benign | 0.2174 | benign | -0.345 | Destabilizing | 0.999 | D | 0.479 | neutral | N | 0.477382719 | None | None | I |
| L/K | 0.7814 | likely_pathogenic | 0.7494 | pathogenic | -0.407 | Destabilizing | 1.0 | D | 0.675 | neutral | None | None | None | None | I |
| L/M | 0.2452 | likely_benign | 0.2557 | benign | -0.59 | Destabilizing | 1.0 | D | 0.543 | neutral | None | None | None | None | I |
| L/N | 0.8679 | likely_pathogenic | 0.8424 | pathogenic | -0.315 | Destabilizing | 1.0 | D | 0.731 | prob.delet. | None | None | None | None | I |
| L/P | 0.9608 | likely_pathogenic | 0.9605 | pathogenic | -0.438 | Destabilizing | 1.0 | D | 0.731 | prob.delet. | None | None | None | None | I |
| L/Q | 0.6213 | likely_pathogenic | 0.5821 | pathogenic | -0.471 | Destabilizing | 1.0 | D | 0.686 | prob.neutral | None | None | None | None | I |
| L/R | 0.6217 | likely_pathogenic | 0.5838 | pathogenic | 0.117 | Stabilizing | 1.0 | D | 0.693 | prob.neutral | None | None | None | None | I |
| L/S | 0.8616 | likely_pathogenic | 0.8377 | pathogenic | -0.778 | Destabilizing | 1.0 | D | 0.671 | neutral | N | 0.516091858 | None | None | I |
| L/T | 0.7645 | likely_pathogenic | 0.7192 | pathogenic | -0.719 | Destabilizing | 1.0 | D | 0.603 | neutral | None | None | None | None | I |
| L/V | 0.2799 | likely_benign | 0.2784 | benign | -0.438 | Destabilizing | 0.999 | D | 0.535 | neutral | N | 0.521481822 | None | None | I |
| L/W | 0.7238 | likely_pathogenic | 0.7173 | pathogenic | -0.6 | Destabilizing | 1.0 | D | 0.709 | prob.delet. | None | None | None | None | I |
| L/Y | 0.758 | likely_pathogenic | 0.7531 | pathogenic | -0.372 | Destabilizing | 1.0 | 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.