Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31874 | 95845;95846;95847 | chr2:178545490;178545489;178545488 | chr2:179410217;179410216;179410215 |
| N2AB | 30233 | 90922;90923;90924 | chr2:178545490;178545489;178545488 | chr2:179410217;179410216;179410215 |
| N2A | 29306 | 88141;88142;88143 | chr2:178545490;178545489;178545488 | chr2:179410217;179410216;179410215 |
| N2B | 22809 | 68650;68651;68652 | chr2:178545490;178545489;178545488 | chr2:179410217;179410216;179410215 |
| Novex-1 | 22934 | 69025;69026;69027 | chr2:178545490;178545489;178545488 | chr2:179410217;179410216;179410215 |
| Novex-2 | 23001 | 69226;69227;69228 | chr2:178545490;178545489;178545488 | chr2:179410217;179410216;179410215 |
| 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/R | rs1405952396  |
0.704 | 0.784 | N | 0.437 | 0.35 | 0.526437037968 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| M/T | None | None | 0.784 | N | 0.376 | 0.303 | 0.659202117215 | gnomAD-4.0.0 | 1.59179E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85968E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.2217 | likely_benign | 0.2663 | benign | -1.132 | Destabilizing | 0.495 | N | 0.377 | neutral | None | None | None | None | N |
| M/C | 0.6122 | likely_pathogenic | 0.6972 | pathogenic | -0.695 | Destabilizing | 0.981 | D | 0.398 | neutral | None | None | None | None | N |
| M/D | 0.7745 | likely_pathogenic | 0.8151 | pathogenic | -0.05 | Destabilizing | 0.981 | D | 0.395 | neutral | None | None | None | None | N |
| M/E | 0.4336 | ambiguous | 0.4808 | ambiguous | -0.06 | Destabilizing | 0.936 | D | 0.392 | neutral | None | None | None | None | N |
| M/F | 0.305 | likely_benign | 0.3575 | ambiguous | -0.436 | Destabilizing | 0.704 | D | 0.311 | neutral | None | None | None | None | N |
| M/G | 0.4414 | ambiguous | 0.5153 | ambiguous | -1.374 | Destabilizing | 0.936 | D | 0.417 | neutral | None | None | None | None | N |
| M/H | 0.3673 | ambiguous | 0.4121 | ambiguous | -0.359 | Destabilizing | 0.995 | D | 0.345 | neutral | None | None | None | None | N |
| M/I | 0.2162 | likely_benign | 0.2515 | benign | -0.549 | Destabilizing | 0.139 | N | 0.266 | neutral | N | 0.327042016 | None | None | N |
| M/K | 0.1572 | likely_benign | 0.1497 | benign | -0.056 | Destabilizing | 0.784 | D | 0.383 | neutral | N | 0.347606502 | None | None | N |
| M/L | 0.0803 | likely_benign | 0.0871 | benign | -0.549 | Destabilizing | 0.001 | N | 0.104 | neutral | N | 0.388762479 | None | None | N |
| M/N | 0.3737 | ambiguous | 0.4257 | ambiguous | 0.085 | Stabilizing | 0.981 | D | 0.385 | neutral | None | None | None | None | N |
| M/P | 0.6026 | likely_pathogenic | 0.6742 | pathogenic | -0.716 | Destabilizing | 0.981 | D | 0.387 | neutral | None | None | None | None | N |
| M/Q | 0.1557 | likely_benign | 0.1731 | benign | -0.039 | Destabilizing | 0.981 | D | 0.383 | neutral | None | None | None | None | N |
| M/R | 0.1648 | likely_benign | 0.1558 | benign | 0.488 | Stabilizing | 0.784 | D | 0.437 | neutral | N | 0.357476779 | None | None | N |
| M/S | 0.2671 | likely_benign | 0.317 | benign | -0.45 | Destabilizing | 0.828 | D | 0.381 | neutral | None | None | None | None | N |
| M/T | 0.1218 | likely_benign | 0.1373 | benign | -0.35 | Destabilizing | 0.784 | D | 0.376 | neutral | N | 0.311475131 | None | None | N |
| M/V | 0.0807 | likely_benign | 0.0885 | benign | -0.716 | Destabilizing | 0.139 | N | 0.192 | neutral | N | 0.369619357 | None | None | N |
| M/W | 0.5252 | ambiguous | 0.582 | pathogenic | -0.358 | Destabilizing | 0.995 | D | 0.385 | neutral | None | None | None | None | N |
| M/Y | 0.5114 | ambiguous | 0.5686 | pathogenic | -0.32 | Destabilizing | 0.981 | D | 0.433 | 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.