Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 997 | 3214;3215;3216 | chr2:178782917;178782916;178782915 | chr2:179647644;179647643;179647642 |
| N2AB | 997 | 3214;3215;3216 | chr2:178782917;178782916;178782915 | chr2:179647644;179647643;179647642 |
| N2A | 997 | 3214;3215;3216 | chr2:178782917;178782916;178782915 | chr2:179647644;179647643;179647642 |
| N2B | 951 | 3076;3077;3078 | chr2:178782917;178782916;178782915 | chr2:179647644;179647643;179647642 |
| Novex-1 | 951 | 3076;3077;3078 | chr2:178782917;178782916;178782915 | chr2:179647644;179647643;179647642 |
| Novex-2 | 951 | 3076;3077;3078 | chr2:178782917;178782916;178782915 | chr2:179647644;179647643;179647642 |
| Novex-3 | 997 | 3214;3215;3216 | chr2:178782917;178782916;178782915 | chr2:179647644;179647643;179647642 |
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/V | rs761499989  |
-1.217 | 0.001 | N | 0.118 | 0.063 | 0.518531843619 | gnomAD-2.1.1 | 1.2E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 1.77E-05 | 0 |
| I/V | rs761499989 |
-1.217 | 0.001 | N | 0.118 | 0.063 | 0.518531843619 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| I/V | rs761499989 |
-1.217 | 0.001 | N | 0.118 | 0.063 | 0.518531843619 | gnomAD-4.0.0 | 6.403E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 7.17521E-06 | 2.67996E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.4915 | ambiguous | 0.4108 | ambiguous | -2.057 | Highly Destabilizing | 0.001 | N | 0.186 | neutral | None | None | None | None | N |
| I/C | 0.8488 | likely_pathogenic | 0.8234 | pathogenic | -1.044 | Destabilizing | 0.836 | D | 0.471 | neutral | None | None | None | None | N |
| I/D | 0.8608 | likely_pathogenic | 0.8197 | pathogenic | -1.687 | Destabilizing | 0.836 | D | 0.547 | neutral | None | None | None | None | N |
| I/E | 0.6968 | likely_pathogenic | 0.6249 | pathogenic | -1.648 | Destabilizing | 0.418 | N | 0.535 | neutral | None | None | None | None | N |
| I/F | 0.2415 | likely_benign | 0.2184 | benign | -1.424 | Destabilizing | 0.002 | N | 0.199 | neutral | N | 0.503765598 | None | None | N |
| I/G | 0.8595 | likely_pathogenic | 0.8186 | pathogenic | -2.425 | Highly Destabilizing | 0.264 | N | 0.52 | neutral | None | None | None | None | N |
| I/H | 0.6324 | likely_pathogenic | 0.5908 | pathogenic | -1.669 | Destabilizing | 0.716 | D | 0.543 | neutral | None | None | None | None | N |
| I/K | 0.4453 | ambiguous | 0.3792 | ambiguous | -1.366 | Destabilizing | 0.418 | N | 0.539 | neutral | None | None | None | None | N |
| I/L | 0.2137 | likely_benign | 0.1983 | benign | -1.081 | Destabilizing | 0.001 | N | 0.14 | neutral | N | 0.479595326 | None | None | N |
| I/M | 0.1491 | likely_benign | 0.1401 | benign | -0.723 | Destabilizing | 0.047 | N | 0.285 | neutral | N | 0.5078678 | None | None | N |
| I/N | 0.4633 | ambiguous | 0.397 | ambiguous | -1.187 | Destabilizing | 0.794 | D | 0.551 | neutral | N | 0.485783339 | None | None | N |
| I/P | 0.9667 | likely_pathogenic | 0.9663 | pathogenic | -1.379 | Destabilizing | 0.836 | D | 0.547 | neutral | None | None | None | None | N |
| I/Q | 0.5821 | likely_pathogenic | 0.523 | ambiguous | -1.35 | Destabilizing | 0.836 | D | 0.554 | neutral | None | None | None | None | N |
| I/R | 0.3749 | ambiguous | 0.329 | benign | -0.769 | Destabilizing | 0.716 | D | 0.545 | neutral | None | None | None | None | N |
| I/S | 0.4821 | ambiguous | 0.4137 | ambiguous | -1.82 | Destabilizing | 0.213 | N | 0.458 | neutral | N | 0.47933944 | None | None | N |
| I/T | 0.2283 | likely_benign | 0.1765 | benign | -1.671 | Destabilizing | 0.351 | N | 0.435 | neutral | N | 0.47194436 | None | None | N |
| I/V | 0.0903 | likely_benign | 0.0814 | benign | -1.379 | Destabilizing | 0.001 | N | 0.118 | neutral | N | 0.431022824 | None | None | N |
| I/W | 0.8355 | likely_pathogenic | 0.8372 | pathogenic | -1.57 | Destabilizing | 0.951 | D | 0.521 | neutral | None | None | None | None | N |
| I/Y | 0.6015 | likely_pathogenic | 0.5642 | pathogenic | -1.358 | Destabilizing | 0.004 | N | 0.179 | 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.