Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29599 | 89020;89021;89022 | chr2:178554552;178554551;178554550 | chr2:179419279;179419278;179419277 |
| N2AB | 27958 | 84097;84098;84099 | chr2:178554552;178554551;178554550 | chr2:179419279;179419278;179419277 |
| N2A | 27031 | 81316;81317;81318 | chr2:178554552;178554551;178554550 | chr2:179419279;179419278;179419277 |
| N2B | 20534 | 61825;61826;61827 | chr2:178554552;178554551;178554550 | chr2:179419279;179419278;179419277 |
| Novex-1 | 20659 | 62200;62201;62202 | chr2:178554552;178554551;178554550 | chr2:179419279;179419278;179419277 |
| Novex-2 | 20726 | 62401;62402;62403 | chr2:178554552;178554551;178554550 | chr2:179419279;179419278;179419277 |
| 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/M | rs771722266  |
-0.582 | 1.0 | N | 0.609 | 0.256 | 0.386395597597 | gnomAD-2.1.1 | 7.14E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.56E-05 | 0 |
| I/M | rs771722266 |
-0.582 | 1.0 | N | 0.609 | 0.256 | 0.386395597597 | gnomAD-4.0.0 | 9.5787E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.2592E-05 | 0 | 0 |
| I/T | None | None | 1.0 | N | 0.57 | 0.38 | 0.641834116846 | gnomAD-4.0.0 | 2.05257E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79886E-06 | 1.15934E-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 | 0.9545 | likely_pathogenic | 0.9332 | pathogenic | -1.005 | Destabilizing | 0.999 | D | 0.437 | neutral | None | None | None | None | N |
| I/C | 0.9792 | likely_pathogenic | 0.9692 | pathogenic | -0.872 | Destabilizing | 1.0 | D | 0.617 | neutral | None | None | None | None | N |
| I/D | 0.996 | likely_pathogenic | 0.9929 | pathogenic | -0.214 | Destabilizing | 1.0 | D | 0.665 | neutral | None | None | None | None | N |
| I/E | 0.9839 | likely_pathogenic | 0.9722 | pathogenic | -0.235 | Destabilizing | 1.0 | D | 0.669 | neutral | None | None | None | None | N |
| I/F | 0.6628 | likely_pathogenic | 0.6118 | pathogenic | -0.648 | Destabilizing | 1.0 | D | 0.627 | neutral | N | 0.472596552 | None | None | N |
| I/G | 0.9873 | likely_pathogenic | 0.9799 | pathogenic | -1.251 | Destabilizing | 1.0 | D | 0.668 | neutral | None | None | None | None | N |
| I/H | 0.9661 | likely_pathogenic | 0.9468 | pathogenic | -0.255 | Destabilizing | 1.0 | D | 0.648 | neutral | None | None | None | None | N |
| I/K | 0.9379 | likely_pathogenic | 0.9078 | pathogenic | -0.599 | Destabilizing | 1.0 | D | 0.665 | neutral | None | None | None | None | N |
| I/L | 0.2319 | likely_benign | 0.2216 | benign | -0.435 | Destabilizing | 0.993 | D | 0.246 | neutral | N | 0.493793788 | None | None | N |
| I/M | 0.3609 | ambiguous | 0.3247 | benign | -0.586 | Destabilizing | 1.0 | D | 0.609 | neutral | N | 0.520673745 | None | None | N |
| I/N | 0.947 | likely_pathogenic | 0.9117 | pathogenic | -0.531 | Destabilizing | 1.0 | D | 0.679 | prob.neutral | N | 0.503741423 | None | None | N |
| I/P | 0.9789 | likely_pathogenic | 0.9733 | pathogenic | -0.592 | Destabilizing | 1.0 | D | 0.681 | prob.neutral | None | None | None | None | N |
| I/Q | 0.9248 | likely_pathogenic | 0.8858 | pathogenic | -0.663 | Destabilizing | 1.0 | D | 0.657 | neutral | None | None | None | None | N |
| I/R | 0.8846 | likely_pathogenic | 0.8351 | pathogenic | -0.048 | Destabilizing | 1.0 | D | 0.68 | prob.neutral | None | None | None | None | N |
| I/S | 0.9484 | likely_pathogenic | 0.9194 | pathogenic | -1.11 | Destabilizing | 1.0 | D | 0.637 | neutral | N | 0.479421768 | None | None | N |
| I/T | 0.9387 | likely_pathogenic | 0.9033 | pathogenic | -1.007 | Destabilizing | 1.0 | D | 0.57 | neutral | N | 0.476400106 | None | None | N |
| I/V | 0.3878 | ambiguous | 0.3304 | benign | -0.592 | Destabilizing | 0.993 | D | 0.242 | neutral | N | 0.470436926 | None | None | N |
| I/W | 0.9668 | likely_pathogenic | 0.9556 | pathogenic | -0.658 | Destabilizing | 1.0 | D | 0.693 | prob.neutral | None | None | None | None | N |
| I/Y | 0.9453 | likely_pathogenic | 0.9176 | pathogenic | -0.438 | Destabilizing | 1.0 | D | 0.655 | 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.