Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19581 | 58966;58967;58968 | chr2:178593467;178593466;178593465 | chr2:179458194;179458193;179458192 |
| N2AB | 17940 | 54043;54044;54045 | chr2:178593467;178593466;178593465 | chr2:179458194;179458193;179458192 |
| N2A | 17013 | 51262;51263;51264 | chr2:178593467;178593466;178593465 | chr2:179458194;179458193;179458192 |
| N2B | 10516 | 31771;31772;31773 | chr2:178593467;178593466;178593465 | chr2:179458194;179458193;179458192 |
| Novex-1 | 10641 | 32146;32147;32148 | chr2:178593467;178593466;178593465 | chr2:179458194;179458193;179458192 |
| Novex-2 | 10708 | 32347;32348;32349 | chr2:178593467;178593466;178593465 | chr2:179458194;179458193;179458192 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/E | None | None | 0.003 | N | 0.401 | 0.103 | 0.273503213844 | gnomAD-4.0.0 | 1.37237E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.53203E-05 | None | 0 | 0 | 9.00169E-07 | 0 | 0 |
| D/N | None | None | 0.782 | N | 0.585 | 0.251 | 0.388653054685 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 6.07533E-05 | 0 |
| D/V | rs1421309086  |
None | 0.642 | N | 0.744 | 0.27 | 0.391470661076 | gnomAD-4.0.0 | 1.60233E-06 | None | None | None | None | N | None | 5.77768E-05 | 0 | None | 0 | 0 | None | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.1522 | likely_benign | 0.1043 | benign | -0.307 | Destabilizing | 0.003 | N | 0.58 | neutral | N | 0.506723013 | None | None | N |
| D/C | 0.6216 | likely_pathogenic | 0.5437 | ambiguous | -0.193 | Destabilizing | 0.973 | D | 0.772 | deleterious | None | None | None | None | N |
| D/E | 0.2112 | likely_benign | 0.1693 | benign | -0.719 | Destabilizing | 0.003 | N | 0.401 | neutral | N | 0.485019589 | None | None | N |
| D/F | 0.7021 | likely_pathogenic | 0.5877 | pathogenic | -0.299 | Destabilizing | 0.704 | D | 0.757 | deleterious | None | None | None | None | N |
| D/G | 0.1364 | likely_benign | 0.1122 | benign | -0.604 | Destabilizing | 0.338 | N | 0.608 | neutral | N | 0.464372171 | None | None | N |
| D/H | 0.3636 | ambiguous | 0.2877 | benign | -0.795 | Destabilizing | 0.782 | D | 0.661 | neutral | N | 0.511563313 | None | None | N |
| D/I | 0.5933 | likely_pathogenic | 0.4664 | ambiguous | 0.458 | Stabilizing | 0.826 | D | 0.751 | deleterious | None | None | None | None | N |
| D/K | 0.4943 | ambiguous | 0.4002 | ambiguous | -0.703 | Destabilizing | 0.404 | N | 0.666 | neutral | None | None | None | None | N |
| D/L | 0.4587 | ambiguous | 0.3443 | ambiguous | 0.458 | Stabilizing | 0.704 | D | 0.743 | deleterious | None | None | None | None | N |
| D/M | 0.6804 | likely_pathogenic | 0.5711 | pathogenic | 0.822 | Stabilizing | 0.973 | D | 0.775 | deleterious | None | None | None | None | N |
| D/N | 0.1396 | likely_benign | 0.1103 | benign | -0.786 | Destabilizing | 0.782 | D | 0.585 | neutral | N | 0.48354433 | None | None | N |
| D/P | 0.8594 | likely_pathogenic | 0.7953 | pathogenic | 0.228 | Stabilizing | 0.906 | D | 0.627 | neutral | None | None | None | None | N |
| D/Q | 0.4158 | ambiguous | 0.3385 | benign | -0.666 | Destabilizing | 0.704 | D | 0.554 | neutral | None | None | None | None | N |
| D/R | 0.5501 | ambiguous | 0.4483 | ambiguous | -0.626 | Destabilizing | 0.826 | D | 0.716 | prob.delet. | None | None | None | None | N |
| D/S | 0.1159 | likely_benign | 0.0912 | benign | -1.016 | Destabilizing | 0.404 | N | 0.551 | neutral | None | None | None | None | N |
| D/T | 0.2976 | likely_benign | 0.2296 | benign | -0.8 | Destabilizing | 0.575 | D | 0.665 | neutral | None | None | None | None | N |
| D/V | 0.3594 | ambiguous | 0.2673 | benign | 0.228 | Stabilizing | 0.642 | D | 0.744 | deleterious | N | 0.500967476 | None | None | N |
| D/W | 0.9176 | likely_pathogenic | 0.8858 | pathogenic | -0.337 | Destabilizing | 0.973 | D | 0.783 | deleterious | None | None | None | None | N |
| D/Y | 0.3048 | likely_benign | 0.244 | benign | -0.165 | Destabilizing | 0.007 | N | 0.671 | neutral | N | 0.493966037 | 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.