Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28522 | 85789;85790;85791 | chr2:178560568;178560567;178560566 | chr2:179425295;179425294;179425293 |
| N2AB | 26881 | 80866;80867;80868 | chr2:178560568;178560567;178560566 | chr2:179425295;179425294;179425293 |
| N2A | 25954 | 78085;78086;78087 | chr2:178560568;178560567;178560566 | chr2:179425295;179425294;179425293 |
| N2B | 19457 | 58594;58595;58596 | chr2:178560568;178560567;178560566 | chr2:179425295;179425294;179425293 |
| Novex-1 | 19582 | 58969;58970;58971 | chr2:178560568;178560567;178560566 | chr2:179425295;179425294;179425293 |
| Novex-2 | 19649 | 59170;59171;59172 | chr2:178560568;178560567;178560566 | chr2:179425295;179425294;179425293 |
| 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 | rs372146722  |
-2.337 | 0.892 | N | 0.723 | 0.376 | None | gnomAD-2.1.1 | 8.09E-06 | None | None | None | None | N | None | 0 | 2.91E-05 | None | 0 | 0 | None | 0 | None | 0 | 8.96E-06 | 0 |
| I/T | rs372146722 |
-2.337 | 0.892 | N | 0.723 | 0.376 | None | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| I/T | rs372146722 |
-2.337 | 0.892 | N | 0.723 | 0.376 | None | gnomAD-4.0.0 | 1.36375E-05 | None | None | None | None | N | None | 0 | 3.337E-05 | None | 0 | 0 | None | 0 | 0 | 1.61058E-05 | 0 | 1.60195E-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 | 0.5017 | ambiguous | 0.4889 | ambiguous | -2.501 | Highly Destabilizing | 0.845 | D | 0.684 | prob.neutral | None | None | None | None | N |
| I/C | 0.6177 | likely_pathogenic | 0.6279 | pathogenic | -1.405 | Destabilizing | 0.999 | D | 0.739 | prob.delet. | None | None | None | None | N |
| I/D | 0.8525 | likely_pathogenic | 0.8504 | pathogenic | -3.022 | Highly Destabilizing | 0.996 | D | 0.821 | deleterious | None | None | None | None | N |
| I/E | 0.6557 | likely_pathogenic | 0.681 | pathogenic | -2.745 | Highly Destabilizing | 0.987 | D | 0.794 | deleterious | None | None | None | None | N |
| I/F | 0.2432 | likely_benign | 0.241 | benign | -1.44 | Destabilizing | 0.975 | D | 0.709 | prob.delet. | None | None | None | None | N |
| I/G | 0.8089 | likely_pathogenic | 0.7948 | pathogenic | -3.044 | Highly Destabilizing | 0.987 | D | 0.789 | deleterious | None | None | None | None | N |
| I/H | 0.5356 | ambiguous | 0.5369 | ambiguous | -2.683 | Highly Destabilizing | 0.999 | D | 0.819 | deleterious | None | None | None | None | N |
| I/K | 0.4304 | ambiguous | 0.4467 | ambiguous | -1.713 | Destabilizing | 0.983 | D | 0.794 | deleterious | N | 0.490214765 | None | None | N |
| I/L | 0.1249 | likely_benign | 0.1153 | benign | -0.886 | Destabilizing | 0.426 | N | 0.466 | neutral | N | 0.473554589 | None | None | N |
| I/M | 0.1483 | likely_benign | 0.1428 | benign | -0.909 | Destabilizing | 0.983 | D | 0.712 | prob.delet. | N | 0.494815295 | None | None | N |
| I/N | 0.4112 | ambiguous | 0.415 | ambiguous | -2.239 | Highly Destabilizing | 0.996 | D | 0.848 | deleterious | None | None | None | None | N |
| I/P | 0.977 | likely_pathogenic | 0.9772 | pathogenic | -1.413 | Destabilizing | 0.996 | D | 0.837 | deleterious | None | None | None | None | N |
| I/Q | 0.4548 | ambiguous | 0.4812 | ambiguous | -1.982 | Destabilizing | 0.996 | D | 0.841 | deleterious | None | None | None | None | N |
| I/R | 0.3227 | likely_benign | 0.3343 | benign | -1.657 | Destabilizing | 0.983 | D | 0.847 | deleterious | N | 0.506992372 | None | None | N |
| I/S | 0.3839 | ambiguous | 0.3861 | ambiguous | -2.787 | Highly Destabilizing | 0.987 | D | 0.719 | prob.delet. | None | None | None | None | N |
| I/T | 0.2916 | likely_benign | 0.2828 | benign | -2.374 | Highly Destabilizing | 0.892 | D | 0.723 | prob.delet. | N | 0.484787516 | None | None | N |
| I/V | 0.0761 | likely_benign | 0.0772 | benign | -1.413 | Destabilizing | 0.011 | N | 0.278 | neutral | N | 0.506819013 | None | None | N |
| I/W | 0.8473 | likely_pathogenic | 0.8338 | pathogenic | -1.887 | Destabilizing | 0.999 | D | 0.76 | deleterious | None | None | None | None | N |
| I/Y | 0.517 | ambiguous | 0.5386 | ambiguous | -1.612 | Destabilizing | 0.987 | D | 0.754 | deleterious | 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.