Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30048 | 90367;90368;90369 | chr2:178552758;178552757;178552756 | chr2:179417485;179417484;179417483 |
| N2AB | 28407 | 85444;85445;85446 | chr2:178552758;178552757;178552756 | chr2:179417485;179417484;179417483 |
| N2A | 27480 | 82663;82664;82665 | chr2:178552758;178552757;178552756 | chr2:179417485;179417484;179417483 |
| N2B | 20983 | 63172;63173;63174 | chr2:178552758;178552757;178552756 | chr2:179417485;179417484;179417483 |
| Novex-1 | 21108 | 63547;63548;63549 | chr2:178552758;178552757;178552756 | chr2:179417485;179417484;179417483 |
| Novex-2 | 21175 | 63748;63749;63750 | chr2:178552758;178552757;178552756 | chr2:179417485;179417484;179417483 |
| 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 | rs760605469  |
-1.768 | None | N | 0.209 | 0.074 | 0.236890367714 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.86E-06 | 0 |
| I/T | rs760605469 |
-1.768 | None | N | 0.209 | 0.074 | 0.236890367714 | 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/T | rs760605469 |
-1.768 | None | N | 0.209 | 0.074 | 0.236890367714 | gnomAD-4.0.0 | 1.85892E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.5427E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.1494 | likely_benign | 0.1356 | benign | -2.238 | Highly Destabilizing | 0.002 | N | 0.251 | neutral | None | None | None | None | N |
| I/C | 0.3505 | ambiguous | 0.3331 | benign | -1.713 | Destabilizing | 0.245 | N | 0.491 | neutral | None | None | None | None | N |
| I/D | 0.4773 | ambiguous | 0.4513 | ambiguous | -2.424 | Highly Destabilizing | 0.018 | N | 0.424 | neutral | None | None | None | None | N |
| I/E | 0.3909 | ambiguous | 0.3774 | ambiguous | -2.364 | Highly Destabilizing | 0.004 | N | 0.418 | neutral | None | None | None | None | N |
| I/F | 0.107 | likely_benign | 0.0986 | benign | -1.529 | Destabilizing | 0.033 | N | 0.42 | neutral | N | 0.445965343 | None | None | N |
| I/G | 0.3838 | ambiguous | 0.3403 | ambiguous | -2.618 | Highly Destabilizing | 0.008 | N | 0.433 | neutral | None | None | None | None | N |
| I/H | 0.2078 | likely_benign | 0.1913 | benign | -1.766 | Destabilizing | 0.497 | N | 0.586 | neutral | None | None | None | None | N |
| I/K | 0.1585 | likely_benign | 0.1568 | benign | -1.611 | Destabilizing | None | N | 0.487 | neutral | None | None | None | None | N |
| I/L | 0.0915 | likely_benign | 0.0844 | benign | -1.212 | Destabilizing | 0.001 | N | 0.244 | neutral | N | 0.421682974 | None | None | N |
| I/M | 0.0778 | likely_benign | 0.0742 | benign | -1.11 | Destabilizing | 0.108 | N | 0.476 | neutral | N | 0.452525956 | None | None | N |
| I/N | 0.1278 | likely_benign | 0.1115 | benign | -1.613 | Destabilizing | 0.014 | N | 0.437 | neutral | N | 0.42147233 | None | None | N |
| I/P | 0.8592 | likely_pathogenic | 0.8395 | pathogenic | -1.529 | Destabilizing | 0.037 | N | 0.501 | neutral | None | None | None | None | N |
| I/Q | 0.2047 | likely_benign | 0.1931 | benign | -1.784 | Destabilizing | 0.044 | N | 0.587 | neutral | None | None | None | None | N |
| I/R | 0.1234 | likely_benign | 0.1188 | benign | -1.009 | Destabilizing | 0.009 | N | 0.486 | neutral | None | None | None | None | N |
| I/S | 0.112 | likely_benign | 0.0971 | benign | -2.238 | Highly Destabilizing | None | N | 0.331 | neutral | N | 0.361287876 | None | None | N |
| I/T | 0.0691 | likely_benign | 0.0641 | benign | -2.063 | Highly Destabilizing | None | N | 0.209 | neutral | N | 0.311667132 | None | None | N |
| I/V | 0.0687 | likely_benign | 0.0672 | benign | -1.529 | Destabilizing | None | N | 0.183 | neutral | N | 0.398902114 | None | None | N |
| I/W | 0.5394 | ambiguous | 0.54 | ambiguous | -1.667 | Destabilizing | 0.788 | D | 0.573 | neutral | None | None | None | None | N |
| I/Y | 0.2739 | likely_benign | 0.257 | benign | -1.456 | Destabilizing | 0.085 | N | 0.524 | 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.