Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 33235 | 99928;99929;99930 | chr2:178537504;178537503;178537502 | chr2:179402231;179402230;179402229 |
| N2AB | 31594 | 95005;95006;95007 | chr2:178537504;178537503;178537502 | chr2:179402231;179402230;179402229 |
| N2A | 30667 | 92224;92225;92226 | chr2:178537504;178537503;178537502 | chr2:179402231;179402230;179402229 |
| N2B | 24170 | 72733;72734;72735 | chr2:178537504;178537503;178537502 | chr2:179402231;179402230;179402229 |
| Novex-1 | 24295 | 73108;73109;73110 | chr2:178537504;178537503;178537502 | chr2:179402231;179402230;179402229 |
| Novex-2 | 24362 | 73309;73310;73311 | chr2:178537504;178537503;178537502 | chr2:179402231;179402230;179402229 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/E | None | None | 0.992 | N | 0.669 | 0.446 | 0.399304321381 | gnomAD-4.0.0 | 1.5914E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.77362E-05 | None | 0 | 0 | 0 | 0 | 0 |
| K/Q | rs774189985  |
0.005 | 0.994 | N | 0.668 | 0.415 | 0.366466682447 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.87E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/A | 0.395 | ambiguous | 0.379 | ambiguous | -0.201 | Destabilizing | 0.998 | D | 0.68 | prob.neutral | None | None | None | None | N |
| K/C | 0.7362 | likely_pathogenic | 0.7451 | pathogenic | -0.449 | Destabilizing | 1.0 | D | 0.713 | prob.delet. | None | None | None | None | N |
| K/D | 0.4681 | ambiguous | 0.4529 | ambiguous | 0.139 | Stabilizing | 0.999 | D | 0.691 | prob.neutral | None | None | None | None | N |
| K/E | 0.1611 | likely_benign | 0.1505 | benign | 0.216 | Stabilizing | 0.992 | D | 0.669 | neutral | N | 0.456617558 | None | None | N |
| K/F | 0.7832 | likely_pathogenic | 0.7924 | pathogenic | -0.104 | Destabilizing | 1.0 | D | 0.7 | prob.neutral | None | None | None | None | N |
| K/G | 0.5432 | ambiguous | 0.5324 | ambiguous | -0.484 | Destabilizing | 0.999 | D | 0.649 | neutral | None | None | None | None | N |
| K/H | 0.2509 | likely_benign | 0.2509 | benign | -0.617 | Destabilizing | 1.0 | D | 0.648 | neutral | None | None | None | None | N |
| K/I | 0.3314 | likely_benign | 0.3267 | benign | 0.495 | Stabilizing | 0.977 | D | 0.711 | prob.delet. | N | 0.504027503 | None | None | N |
| K/L | 0.4023 | ambiguous | 0.3876 | ambiguous | 0.495 | Stabilizing | 0.982 | D | 0.649 | neutral | None | None | None | None | N |
| K/M | 0.246 | likely_benign | 0.2338 | benign | 0.062 | Stabilizing | 0.999 | D | 0.641 | neutral | None | None | None | None | N |
| K/N | 0.271 | likely_benign | 0.2598 | benign | -0.159 | Destabilizing | 0.999 | D | 0.685 | prob.neutral | N | 0.514551141 | None | None | N |
| K/P | 0.9059 | likely_pathogenic | 0.8845 | pathogenic | 0.293 | Stabilizing | 0.999 | D | 0.663 | neutral | None | None | None | None | N |
| K/Q | 0.1127 | likely_benign | 0.1086 | benign | -0.188 | Destabilizing | 0.994 | D | 0.668 | neutral | N | 0.487689827 | None | None | N |
| K/R | 0.0961 | likely_benign | 0.0975 | benign | -0.206 | Destabilizing | 0.987 | D | 0.599 | neutral | N | 0.486729822 | None | None | N |
| K/S | 0.3968 | ambiguous | 0.3867 | ambiguous | -0.693 | Destabilizing | 0.998 | D | 0.651 | neutral | None | None | None | None | N |
| K/T | 0.159 | likely_benign | 0.156 | benign | -0.433 | Destabilizing | 0.998 | D | 0.672 | neutral | N | 0.50333407 | None | None | N |
| K/V | 0.3057 | likely_benign | 0.3123 | benign | 0.293 | Stabilizing | 0.987 | D | 0.699 | prob.neutral | None | None | None | None | N |
| K/W | 0.845 | likely_pathogenic | 0.8402 | pathogenic | -0.098 | Destabilizing | 1.0 | D | 0.719 | prob.delet. | None | None | None | None | N |
| K/Y | 0.6084 | likely_pathogenic | 0.5968 | pathogenic | 0.219 | Stabilizing | 0.997 | D | 0.679 | prob.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.