Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 9744 | 29455;29456;29457 | chr2:178706644;178706643;178706642 | chr2:179571371;179571370;179571369 |
| N2AB | 9427 | 28504;28505;28506 | chr2:178706644;178706643;178706642 | chr2:179571371;179571370;179571369 |
| N2A | 8500 | 25723;25724;25725 | chr2:178706644;178706643;178706642 | chr2:179571371;179571370;179571369 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/C | rs375266859  |
-0.896 | 1.0 | None | 0.711 | 0.414 | None | gnomAD-2.1.1 | 5.35E-05 | None | None | None | None | N | None | 0 | 0 | None | 1.93162E-04 | 0 | None | 3.27E-05 | None | 0 | 9.34E-05 | 0 |
| R/C | rs375266859 |
-0.896 | 1.0 | None | 0.711 | 0.414 | None | gnomAD-3.1.2 | 5.26E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 2.88351E-04 | 0 | None | 0 | 0 | 8.82E-05 | 2.07814E-04 | 0 |
| R/C | rs375266859 |
-0.896 | 1.0 | None | 0.711 | 0.414 | None | gnomAD-4.0.0 | 4.27588E-05 | None | None | None | None | N | None | 0 | 3.33456E-05 | None | 1.35153E-04 | 0 | None | 0 | 0 | 5.17018E-05 | 1.09808E-05 | 1.60092E-05 |
| R/G | rs375266859 |
None | 1.0 | None | 0.675 | 0.531 | 0.418964662724 | gnomAD-4.0.0 | 6.84162E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99425E-07 | 0 | 0 |
| R/H | rs760305440 |
-1.388 | 1.0 | None | 0.675 | 0.502 | None | gnomAD-2.1.1 | 1.78E-05 | None | None | None | None | N | None | 4.14E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 3.12E-05 | 0 |
| R/H | rs760305440 |
-1.388 | 1.0 | None | 0.675 | 0.502 | None | gnomAD-3.1.2 | 5.26E-05 | None | None | None | None | N | None | 4.83E-05 | 1.30993E-04 | 0 | 0 | 0 | None | 0 | 0 | 5.88E-05 | 0 | 0 |
| R/H | rs760305440 |
-1.388 | 1.0 | None | 0.675 | 0.502 | None |
Arimura (2009)
Lopes (2013)
| None |
HCM 
|
het | None | None | N | Increases binding of TTN to CARP (Co-IP assay); alters subcellular localisation of CARP (Myc-tag) | None | None | None | None | None | None | None | None | None | None | None |
| R/H | rs760305440 |
-1.388 | 1.0 | None | 0.675 | 0.502 | None | gnomAD-4.0.0 | 5.26723E-05 | None | None | None | None | N | None | 2.67044E-05 | 5.00067E-05 | None | 0 | 2.22787E-05 | None | 0 | 1.64366E-04 | 6.10253E-05 | 2.19573E-05 | 6.40451E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.9894 | likely_pathogenic | 0.9609 | pathogenic | -0.649 | Destabilizing | 0.999 | D | 0.541 | neutral | None | None | None | None | N |
| R/C | 0.9563 | likely_pathogenic | 0.8461 | pathogenic | -0.615 | Destabilizing | 1.0 | D | 0.711 | prob.delet. | None | None | None | None | N |
| R/D | 0.9882 | likely_pathogenic | 0.9696 | pathogenic | 0.061 | Stabilizing | 1.0 | D | 0.676 | prob.neutral | None | None | None | None | N |
| R/E | 0.9733 | likely_pathogenic | 0.9112 | pathogenic | 0.181 | Stabilizing | 0.999 | D | 0.569 | neutral | None | None | None | None | N |
| R/F | 0.9934 | likely_pathogenic | 0.9702 | pathogenic | -0.564 | Destabilizing | 1.0 | D | 0.701 | prob.neutral | None | None | None | None | N |
| R/G | 0.9663 | likely_pathogenic | 0.8836 | pathogenic | -0.945 | Destabilizing | 1.0 | D | 0.675 | neutral | None | None | None | None | N |
| R/H | 0.7704 | likely_pathogenic | 0.5851 | pathogenic | -1.286 | Destabilizing | 1.0 | D | 0.675 | prob.neutral | None | None | None | None | N |
| R/I | 0.9766 | likely_pathogenic | 0.9106 | pathogenic | 0.139 | Stabilizing | 1.0 | D | 0.709 | prob.delet. | None | None | None | None | N |
| R/K | 0.666 | likely_pathogenic | 0.5128 | ambiguous | -0.594 | Destabilizing | 0.998 | D | 0.444 | neutral | None | None | None | None | N |
| R/L | 0.9653 | likely_pathogenic | 0.895 | pathogenic | 0.139 | Stabilizing | 1.0 | D | 0.675 | neutral | None | None | None | None | N |
| R/M | 0.9845 | likely_pathogenic | 0.9327 | pathogenic | -0.222 | Destabilizing | 1.0 | D | 0.686 | prob.neutral | None | None | None | None | N |
| R/N | 0.9775 | likely_pathogenic | 0.9508 | pathogenic | -0.147 | Destabilizing | 1.0 | D | 0.687 | prob.neutral | None | None | None | None | N |
| R/P | 0.9878 | likely_pathogenic | 0.9634 | pathogenic | -0.102 | Destabilizing | 1.0 | D | 0.651 | neutral | None | None | None | None | N |
| R/Q | 0.8336 | likely_pathogenic | 0.6103 | pathogenic | -0.292 | Destabilizing | 1.0 | D | 0.672 | neutral | None | None | None | None | N |
| R/S | 0.9883 | likely_pathogenic | 0.9625 | pathogenic | -0.88 | Destabilizing | 1.0 | D | 0.718 | prob.delet. | None | None | None | None | N |
| R/T | 0.9811 | likely_pathogenic | 0.9353 | pathogenic | -0.578 | Destabilizing | 1.0 | D | 0.714 | prob.delet. | None | None | None | None | N |
| R/V | 0.9856 | likely_pathogenic | 0.9477 | pathogenic | -0.102 | Destabilizing | 1.0 | D | 0.696 | prob.neutral | None | None | None | None | N |
| R/W | 0.9144 | likely_pathogenic | 0.7493 | pathogenic | -0.291 | Destabilizing | 1.0 | D | 0.709 | prob.delet. | None | None | None | None | N |
| R/Y | 0.9814 | likely_pathogenic | 0.9391 | pathogenic | 0.028 | Stabilizing | 1.0 | D | 0.685 | prob.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.