Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20759 | 62500;62501;62502 | chr2:178589450;178589449;178589448 | chr2:179454177;179454176;179454175 |
| N2AB | 19118 | 57577;57578;57579 | chr2:178589450;178589449;178589448 | chr2:179454177;179454176;179454175 |
| N2A | 18191 | 54796;54797;54798 | chr2:178589450;178589449;178589448 | chr2:179454177;179454176;179454175 |
| N2B | 11694 | 35305;35306;35307 | chr2:178589450;178589449;178589448 | chr2:179454177;179454176;179454175 |
| Novex-1 | 11819 | 35680;35681;35682 | chr2:178589450;178589449;178589448 | chr2:179454177;179454176;179454175 |
| Novex-2 | 11886 | 35881;35882;35883 | chr2:178589450;178589449;178589448 | chr2:179454177;179454176;179454175 |
| 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/K | rs562680371  |
0.736 | 0.842 | N | 0.422 | 0.217 | 0.313210971179 | gnomAD-2.1.1 | 5.08061E-04 | None | None | None | None | N | None | 8.27E-05 | 0 | None | 0 | 0 | None | 4.57696E-03 | None | 0 | 0 | 0 |
| E/K | rs562680371 |
0.736 | 0.842 | N | 0.422 | 0.217 | 0.313210971179 | gnomAD-3.1.2 | 2.23608E-04 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 6.63075E-03 | 4.78469E-04 |
| E/K | rs562680371 |
0.736 | 0.842 | N | 0.422 | 0.217 | 0.313210971179 | 1000 genomes | 1.19808E-03 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 6.1E-03 | None |
| E/K | rs562680371 |
0.736 | 0.842 | N | 0.422 | 0.217 | 0.313210971179 | gnomAD-4.0.0 | 2.64661E-04 | None | None | None | None | N | None | 2.66631E-05 | 0 | None | 0 | 0 | None | 0 | 1.6518E-04 | 8.47725E-07 | 4.44723E-03 | 2.88138E-04 |
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 | 0.1511 | likely_benign | 0.1411 | benign | -0.638 | Destabilizing | 0.915 | D | 0.379 | neutral | N | 0.51405163 | None | None | N |
| E/C | 0.9033 | likely_pathogenic | 0.9069 | pathogenic | -0.284 | Destabilizing | 0.998 | D | 0.568 | neutral | None | None | None | None | N |
| E/D | 0.1682 | likely_benign | 0.1701 | benign | -0.68 | Destabilizing | 0.007 | N | 0.113 | neutral | N | 0.442999608 | None | None | N |
| E/F | 0.864 | likely_pathogenic | 0.8691 | pathogenic | -0.284 | Destabilizing | 0.994 | D | 0.525 | neutral | None | None | None | None | N |
| E/G | 0.2954 | likely_benign | 0.2665 | benign | -0.906 | Destabilizing | 0.842 | D | 0.439 | neutral | N | 0.514918422 | None | None | N |
| E/H | 0.7375 | likely_pathogenic | 0.7273 | pathogenic | -0.237 | Destabilizing | 0.981 | D | 0.352 | neutral | None | None | None | None | N |
| E/I | 0.4582 | ambiguous | 0.4893 | ambiguous | 0.059 | Stabilizing | 0.994 | D | 0.577 | neutral | None | None | None | None | N |
| E/K | 0.3823 | ambiguous | 0.3733 | ambiguous | -0.08 | Destabilizing | 0.842 | D | 0.422 | neutral | N | 0.509896604 | None | None | N |
| E/L | 0.5125 | ambiguous | 0.5298 | ambiguous | 0.059 | Stabilizing | 0.981 | D | 0.523 | neutral | None | None | None | None | N |
| E/M | 0.5168 | ambiguous | 0.538 | ambiguous | 0.241 | Stabilizing | 0.998 | D | 0.491 | neutral | None | None | None | None | N |
| E/N | 0.3481 | ambiguous | 0.3323 | benign | -0.497 | Destabilizing | 0.038 | N | 0.1 | neutral | None | None | None | None | N |
| E/P | 0.4292 | ambiguous | 0.4 | ambiguous | -0.152 | Destabilizing | 0.994 | D | 0.483 | neutral | None | None | None | None | N |
| E/Q | 0.2625 | likely_benign | 0.2465 | benign | -0.429 | Destabilizing | 0.915 | D | 0.463 | neutral | N | 0.471996987 | None | None | N |
| E/R | 0.576 | likely_pathogenic | 0.5576 | ambiguous | 0.209 | Stabilizing | 0.981 | D | 0.394 | neutral | None | None | None | None | N |
| E/S | 0.2863 | likely_benign | 0.2596 | benign | -0.689 | Destabilizing | 0.745 | D | 0.348 | neutral | None | None | None | None | N |
| E/T | 0.2674 | likely_benign | 0.244 | benign | -0.471 | Destabilizing | 0.876 | D | 0.32 | neutral | None | None | None | None | N |
| E/V | 0.2687 | likely_benign | 0.2798 | benign | -0.152 | Destabilizing | 0.991 | D | 0.5 | neutral | N | 0.470729539 | None | None | N |
| E/W | 0.9549 | likely_pathogenic | 0.9575 | pathogenic | -0.047 | Destabilizing | 0.998 | D | 0.641 | neutral | None | None | None | None | N |
| E/Y | 0.7833 | likely_pathogenic | 0.7958 | pathogenic | -0.029 | Destabilizing | 0.994 | D | 0.518 | 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.