Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17780 | 53563;53564;53565 | chr2:178607264;178607263;178607262 | chr2:179471991;179471990;179471989 |
| N2AB | 16139 | 48640;48641;48642 | chr2:178607264;178607263;178607262 | chr2:179471991;179471990;179471989 |
| N2A | 15212 | 45859;45860;45861 | chr2:178607264;178607263;178607262 | chr2:179471991;179471990;179471989 |
| N2B | 8715 | 26368;26369;26370 | chr2:178607264;178607263;178607262 | chr2:179471991;179471990;179471989 |
| Novex-1 | 8840 | 26743;26744;26745 | chr2:178607264;178607263;178607262 | chr2:179471991;179471990;179471989 |
| Novex-2 | 8907 | 26944;26945;26946 | chr2:178607264;178607263;178607262 | chr2:179471991;179471990;179471989 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/I | None | None | 0.704 | N | 0.289 | 0.25 | 0.63454643552 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| M/T | rs879003153  |
-0.919 | 0.92 | N | 0.33 | 0.281 | None | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 4.65E-05 | 0 | 0 |
| M/T | rs879003153 |
-0.919 | 0.92 | N | 0.33 | 0.281 | None | gnomAD-4.0.0 | 1.59343E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.88281E-05 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.7817 | likely_pathogenic | 0.847 | pathogenic | -1.774 | Destabilizing | 0.927 | D | 0.314 | neutral | None | None | None | None | N |
| M/C | 0.8058 | likely_pathogenic | 0.8522 | pathogenic | -1.79 | Destabilizing | 0.999 | D | 0.408 | neutral | None | None | None | None | N |
| M/D | 0.9682 | likely_pathogenic | 0.9787 | pathogenic | -1.735 | Destabilizing | 0.884 | D | 0.466 | neutral | None | None | None | None | N |
| M/E | 0.8868 | likely_pathogenic | 0.9269 | pathogenic | -1.679 | Destabilizing | 0.939 | D | 0.411 | neutral | None | None | None | None | N |
| M/F | 0.4964 | ambiguous | 0.5263 | ambiguous | -0.905 | Destabilizing | 0.982 | D | 0.357 | neutral | None | None | None | None | N |
| M/G | 0.8785 | likely_pathogenic | 0.9105 | pathogenic | -2.089 | Highly Destabilizing | 0.939 | D | 0.415 | neutral | None | None | None | None | N |
| M/H | 0.726 | likely_pathogenic | 0.8144 | pathogenic | -1.424 | Destabilizing | 0.991 | D | 0.409 | neutral | None | None | None | None | N |
| M/I | 0.7789 | likely_pathogenic | 0.8579 | pathogenic | -0.944 | Destabilizing | 0.704 | D | 0.289 | neutral | N | 0.478133689 | None | None | N |
| M/K | 0.6797 | likely_pathogenic | 0.7937 | pathogenic | -0.927 | Destabilizing | 0.92 | D | 0.351 | neutral | N | 0.426030001 | None | None | N |
| M/L | 0.2703 | likely_benign | 0.3323 | benign | -0.944 | Destabilizing | 0.015 | N | 0.083 | neutral | N | 0.440788809 | None | None | N |
| M/N | 0.6709 | likely_pathogenic | 0.7363 | pathogenic | -0.941 | Destabilizing | 0.17 | N | 0.306 | neutral | None | None | None | None | N |
| M/P | 0.998 | likely_pathogenic | 0.9982 | pathogenic | -1.197 | Destabilizing | 0.997 | D | 0.443 | neutral | None | None | None | None | N |
| M/Q | 0.548 | ambiguous | 0.6564 | pathogenic | -1.028 | Destabilizing | 0.991 | D | 0.357 | neutral | None | None | None | None | N |
| M/R | 0.6961 | likely_pathogenic | 0.8096 | pathogenic | -0.571 | Destabilizing | 0.959 | D | 0.42 | neutral | N | 0.426723434 | None | None | N |
| M/S | 0.6879 | likely_pathogenic | 0.7671 | pathogenic | -1.439 | Destabilizing | 0.939 | D | 0.316 | neutral | None | None | None | None | N |
| M/T | 0.5782 | likely_pathogenic | 0.7081 | pathogenic | -1.285 | Destabilizing | 0.92 | D | 0.33 | neutral | N | 0.387202254 | None | None | N |
| M/V | 0.3102 | likely_benign | 0.404 | ambiguous | -1.197 | Destabilizing | 0.704 | D | 0.301 | neutral | N | 0.4528326 | None | None | N |
| M/W | 0.8646 | likely_pathogenic | 0.8939 | pathogenic | -1.002 | Destabilizing | 0.999 | D | 0.416 | neutral | None | None | None | None | N |
| M/Y | 0.7082 | likely_pathogenic | 0.7472 | pathogenic | -0.931 | Destabilizing | 0.997 | D | 0.429 | 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.