Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17112 | 51559;51560;51561 | chr2:178610192;178610191;178610190 | chr2:179474919;179474918;179474917 |
| N2AB | 15471 | 46636;46637;46638 | chr2:178610192;178610191;178610190 | chr2:179474919;179474918;179474917 |
| N2A | 14544 | 43855;43856;43857 | chr2:178610192;178610191;178610190 | chr2:179474919;179474918;179474917 |
| N2B | 8047 | 24364;24365;24366 | chr2:178610192;178610191;178610190 | chr2:179474919;179474918;179474917 |
| Novex-1 | 8172 | 24739;24740;24741 | chr2:178610192;178610191;178610190 | chr2:179474919;179474918;179474917 |
| Novex-2 | 8239 | 24940;24941;24942 | chr2:178610192;178610191;178610190 | chr2:179474919;179474918;179474917 |
| 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/L | None | None | 0.993 | N | 0.259 | 0.27 | 0.545825192673 | gnomAD-4.0.0 | 6.84859E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.00357E-07 | 0 | 0 |
| I/T | rs776500262  |
-0.785 | 1.0 | N | 0.597 | 0.402 | 0.613098244845 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 6.46E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/T | rs776500262 |
-0.785 | 1.0 | N | 0.597 | 0.402 | 0.613098244845 | gnomAD-4.0.0 | 4.79143E-06 | None | None | None | None | N | None | 5.98516E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79957E-06 | 3.47883E-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 | 0.8643 | likely_pathogenic | 0.8705 | pathogenic | -1.036 | Destabilizing | 0.999 | D | 0.449 | neutral | None | None | None | None | N |
| I/C | 0.9401 | likely_pathogenic | 0.9516 | pathogenic | -0.75 | Destabilizing | 1.0 | D | 0.629 | neutral | None | None | None | None | N |
| I/D | 0.973 | likely_pathogenic | 0.9786 | pathogenic | -0.064 | Destabilizing | 1.0 | D | 0.683 | prob.neutral | None | None | None | None | N |
| I/E | 0.9362 | likely_pathogenic | 0.9382 | pathogenic | -0.086 | Destabilizing | 1.0 | D | 0.686 | prob.neutral | None | None | None | None | N |
| I/F | 0.3804 | ambiguous | 0.4354 | ambiguous | -0.683 | Destabilizing | 1.0 | D | 0.644 | neutral | None | None | None | None | N |
| I/G | 0.9591 | likely_pathogenic | 0.9646 | pathogenic | -1.299 | Destabilizing | 1.0 | D | 0.686 | prob.neutral | None | None | None | None | N |
| I/H | 0.8703 | likely_pathogenic | 0.8953 | pathogenic | -0.406 | Destabilizing | 1.0 | D | 0.662 | neutral | None | None | None | None | N |
| I/K | 0.8794 | likely_pathogenic | 0.8838 | pathogenic | -0.518 | Destabilizing | 1.0 | D | 0.683 | prob.neutral | N | 0.459371783 | None | None | N |
| I/L | 0.1777 | likely_benign | 0.1678 | benign | -0.423 | Destabilizing | 0.993 | D | 0.259 | neutral | N | 0.452581884 | None | None | N |
| I/M | 0.2376 | likely_benign | 0.2374 | benign | -0.485 | Destabilizing | 1.0 | D | 0.617 | neutral | N | 0.487811965 | None | None | N |
| I/N | 0.7562 | likely_pathogenic | 0.7825 | pathogenic | -0.367 | Destabilizing | 1.0 | D | 0.694 | prob.neutral | None | None | None | None | N |
| I/P | 0.9389 | likely_pathogenic | 0.9513 | pathogenic | -0.594 | Destabilizing | 1.0 | D | 0.698 | prob.neutral | None | None | None | None | N |
| I/Q | 0.8255 | likely_pathogenic | 0.8302 | pathogenic | -0.503 | Destabilizing | 1.0 | D | 0.675 | prob.neutral | None | None | None | None | N |
| I/R | 0.8401 | likely_pathogenic | 0.8427 | pathogenic | -0.012 | Destabilizing | 1.0 | D | 0.696 | prob.neutral | N | 0.471127572 | None | None | N |
| I/S | 0.811 | likely_pathogenic | 0.8357 | pathogenic | -0.986 | Destabilizing | 1.0 | D | 0.666 | neutral | None | None | None | None | N |
| I/T | 0.8154 | likely_pathogenic | 0.837 | pathogenic | -0.882 | Destabilizing | 1.0 | D | 0.597 | neutral | N | 0.44030602 | None | None | N |
| I/V | 0.2517 | likely_benign | 0.2486 | benign | -0.594 | Destabilizing | 0.993 | D | 0.256 | neutral | N | 0.447810782 | None | None | N |
| I/W | 0.9241 | likely_pathogenic | 0.9486 | pathogenic | -0.7 | Destabilizing | 1.0 | D | 0.693 | prob.neutral | None | None | None | None | N |
| I/Y | 0.7698 | likely_pathogenic | 0.8196 | pathogenic | -0.465 | Destabilizing | 1.0 | D | 0.669 | 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.