Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19533 | 58822;58823;58824 | chr2:178593703;178593702;178593701 | chr2:179458430;179458429;179458428 |
| N2AB | 17892 | 53899;53900;53901 | chr2:178593703;178593702;178593701 | chr2:179458430;179458429;179458428 |
| N2A | 16965 | 51118;51119;51120 | chr2:178593703;178593702;178593701 | chr2:179458430;179458429;179458428 |
| N2B | 10468 | 31627;31628;31629 | chr2:178593703;178593702;178593701 | chr2:179458430;179458429;179458428 |
| Novex-1 | 10593 | 32002;32003;32004 | chr2:178593703;178593702;178593701 | chr2:179458430;179458429;179458428 |
| Novex-2 | 10660 | 32203;32204;32205 | chr2:178593703;178593702;178593701 | chr2:179458430;179458429;179458428 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/P | rs751194562  |
0.015 | 0.667 | N | 0.541 | 0.106 | 0.245660935333 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.91E-06 | 0 |
| A/P | rs751194562 |
0.015 | 0.667 | N | 0.541 | 0.106 | 0.245660935333 | gnomAD-4.0.0 | 3.18433E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.71866E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.533 | ambiguous | 0.5568 | ambiguous | -0.711 | Destabilizing | 0.909 | D | 0.518 | neutral | None | None | None | None | I |
| A/D | 0.6953 | likely_pathogenic | 0.6683 | pathogenic | -0.355 | Destabilizing | 0.272 | N | 0.525 | neutral | None | None | None | None | I |
| A/E | 0.6332 | likely_pathogenic | 0.6068 | pathogenic | -0.517 | Destabilizing | 0.22 | N | 0.521 | neutral | N | 0.470244925 | None | None | I |
| A/F | 0.545 | ambiguous | 0.5575 | ambiguous | -0.927 | Destabilizing | 0.726 | D | 0.599 | neutral | None | None | None | None | I |
| A/G | 0.2442 | likely_benign | 0.2147 | benign | -0.231 | Destabilizing | 0.104 | N | 0.458 | neutral | N | 0.45891321 | None | None | I |
| A/H | 0.7215 | likely_pathogenic | 0.7354 | pathogenic | -0.297 | Destabilizing | 0.968 | D | 0.613 | neutral | None | None | None | None | I |
| A/I | 0.4747 | ambiguous | 0.5093 | ambiguous | -0.352 | Destabilizing | 0.396 | N | 0.543 | neutral | None | None | None | None | I |
| A/K | 0.807 | likely_pathogenic | 0.8011 | pathogenic | -0.4 | Destabilizing | 0.272 | N | 0.525 | neutral | None | None | None | None | I |
| A/L | 0.3215 | likely_benign | 0.3509 | ambiguous | -0.352 | Destabilizing | 0.157 | N | 0.487 | neutral | None | None | None | None | I |
| A/M | 0.4072 | ambiguous | 0.4152 | ambiguous | -0.303 | Destabilizing | 0.909 | D | 0.569 | neutral | None | None | None | None | I |
| A/N | 0.4418 | ambiguous | 0.4451 | ambiguous | -0.138 | Destabilizing | 0.567 | D | 0.531 | neutral | None | None | None | None | I |
| A/P | 0.702 | likely_pathogenic | 0.7617 | pathogenic | -0.274 | Destabilizing | 0.667 | D | 0.541 | neutral | N | 0.47959234 | None | None | I |
| A/Q | 0.5834 | likely_pathogenic | 0.6034 | pathogenic | -0.44 | Destabilizing | 0.726 | D | 0.571 | neutral | None | None | None | None | I |
| A/R | 0.7043 | likely_pathogenic | 0.7034 | pathogenic | 0.024 | Stabilizing | 0.567 | D | 0.565 | neutral | None | None | None | None | I |
| A/S | 0.1207 | likely_benign | 0.1139 | benign | -0.331 | Destabilizing | 0.005 | N | 0.149 | neutral | N | 0.407097523 | None | None | I |
| A/T | 0.1393 | likely_benign | 0.1303 | benign | -0.417 | Destabilizing | 0.001 | N | 0.253 | neutral | N | 0.411524695 | None | None | I |
| A/V | 0.2423 | likely_benign | 0.2436 | benign | -0.274 | Destabilizing | 0.124 | N | 0.428 | neutral | N | 0.440327449 | None | None | I |
| A/W | 0.8942 | likely_pathogenic | 0.9082 | pathogenic | -1.039 | Destabilizing | 0.968 | D | 0.703 | prob.neutral | None | None | None | None | I |
| A/Y | 0.6849 | likely_pathogenic | 0.694 | pathogenic | -0.678 | Destabilizing | 0.726 | D | 0.607 | neutral | None | None | None | None | I |
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.