Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17536 | 52831;52832;52833 | chr2:178608277;178608276;178608275 | chr2:179473004;179473003;179473002 |
| N2AB | 15895 | 47908;47909;47910 | chr2:178608277;178608276;178608275 | chr2:179473004;179473003;179473002 |
| N2A | 14968 | 45127;45128;45129 | chr2:178608277;178608276;178608275 | chr2:179473004;179473003;179473002 |
| N2B | 8471 | 25636;25637;25638 | chr2:178608277;178608276;178608275 | chr2:179473004;179473003;179473002 |
| Novex-1 | 8596 | 26011;26012;26013 | chr2:178608277;178608276;178608275 | chr2:179473004;179473003;179473002 |
| Novex-2 | 8663 | 26212;26213;26214 | chr2:178608277;178608276;178608275 | chr2:179473004;179473003;179473002 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| E/G | rs776023005  |
-0.945 | 1.0 | N | 0.577 | 0.518 | 0.475506082792 | gnomAD-2.1.1 | 4.06E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.98E-06 | 0 |
| E/G | rs776023005 |
-0.945 | 1.0 | N | 0.577 | 0.518 | 0.475506082792 | gnomAD-4.0.0 | 1.59565E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86451E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| E/A | 0.5407 | ambiguous | 0.5856 | pathogenic | -0.523 | Destabilizing | 0.999 | D | 0.627 | neutral | N | 0.474531882 | None | None | N |
| E/C | 0.9767 | likely_pathogenic | 0.9818 | pathogenic | 0.066 | Stabilizing | 1.0 | D | 0.649 | neutral | None | None | None | None | N |
| E/D | 0.5316 | ambiguous | 0.5266 | ambiguous | -0.483 | Destabilizing | 0.999 | D | 0.6 | neutral | N | 0.49618499 | None | None | N |
| E/F | 0.9894 | likely_pathogenic | 0.9922 | pathogenic | -0.545 | Destabilizing | 1.0 | D | 0.61 | neutral | None | None | None | None | N |
| E/G | 0.6605 | likely_pathogenic | 0.7316 | pathogenic | -0.74 | Destabilizing | 1.0 | D | 0.577 | neutral | N | 0.504173934 | None | None | N |
| E/H | 0.9163 | likely_pathogenic | 0.9293 | pathogenic | -0.598 | Destabilizing | 1.0 | D | 0.61 | neutral | None | None | None | None | N |
| E/I | 0.9199 | likely_pathogenic | 0.9369 | pathogenic | 0.021 | Stabilizing | 1.0 | D | 0.617 | neutral | None | None | None | None | N |
| E/K | 0.6458 | likely_pathogenic | 0.6962 | pathogenic | 0.147 | Stabilizing | 0.999 | D | 0.692 | prob.neutral | N | 0.484802232 | None | None | N |
| E/L | 0.9319 | likely_pathogenic | 0.9453 | pathogenic | 0.021 | Stabilizing | 1.0 | D | 0.603 | neutral | None | None | None | None | N |
| E/M | 0.9366 | likely_pathogenic | 0.9496 | pathogenic | 0.365 | Stabilizing | 1.0 | D | 0.578 | neutral | None | None | None | None | N |
| E/N | 0.8235 | likely_pathogenic | 0.8313 | pathogenic | -0.086 | Destabilizing | 1.0 | D | 0.661 | neutral | None | None | None | None | N |
| E/P | 0.7008 | likely_pathogenic | 0.7314 | pathogenic | -0.14 | Destabilizing | 1.0 | D | 0.575 | neutral | None | None | None | None | N |
| E/Q | 0.439 | ambiguous | 0.4839 | ambiguous | -0.058 | Destabilizing | 1.0 | D | 0.663 | neutral | N | 0.476003594 | None | None | N |
| E/R | 0.7495 | likely_pathogenic | 0.7838 | pathogenic | 0.234 | Stabilizing | 1.0 | D | 0.655 | neutral | None | None | None | None | N |
| E/S | 0.6704 | likely_pathogenic | 0.7112 | pathogenic | -0.272 | Destabilizing | 0.999 | D | 0.674 | neutral | None | None | None | None | N |
| E/T | 0.7979 | likely_pathogenic | 0.8369 | pathogenic | -0.1 | Destabilizing | 1.0 | D | 0.613 | neutral | None | None | None | None | N |
| E/V | 0.8004 | likely_pathogenic | 0.8331 | pathogenic | -0.14 | Destabilizing | 1.0 | D | 0.583 | neutral | N | 0.498324584 | None | None | N |
| E/W | 0.9946 | likely_pathogenic | 0.9958 | pathogenic | -0.431 | Destabilizing | 1.0 | D | 0.651 | neutral | None | None | None | None | N |
| E/Y | 0.9752 | likely_pathogenic | 0.9813 | pathogenic | -0.317 | Destabilizing | 1.0 | D | 0.579 | 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.