Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24752 | 74479;74480;74481 | chr2:178571878;178571877;178571876 | chr2:179436605;179436604;179436603 |
| N2AB | 23111 | 69556;69557;69558 | chr2:178571878;178571877;178571876 | chr2:179436605;179436604;179436603 |
| N2A | 22184 | 66775;66776;66777 | chr2:178571878;178571877;178571876 | chr2:179436605;179436604;179436603 |
| N2B | 15687 | 47284;47285;47286 | chr2:178571878;178571877;178571876 | chr2:179436605;179436604;179436603 |
| Novex-1 | 15812 | 47659;47660;47661 | chr2:178571878;178571877;178571876 | chr2:179436605;179436604;179436603 |
| Novex-2 | 15879 | 47860;47861;47862 | chr2:178571878;178571877;178571876 | chr2:179436605;179436604;179436603 |
| 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 | 0.058 | N | 0.374 | 0.156 | 0.139678290688 | gnomAD-4.0.0 | 1.5919E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.02572E-05 |
| D/G | rs775906538  |
-0.038 | 0.006 | N | 0.354 | 0.234 | 0.119812018005 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| D/G | rs775906538 |
-0.038 | 0.006 | N | 0.354 | 0.234 | 0.119812018005 | gnomAD-4.0.0 | 1.59189E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43299E-05 | 0 |
| D/N | None | None | 0.822 | N | 0.477 | 0.389 | 0.181679512989 | gnomAD-4.0.0 | 7.52769E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.89563E-06 | 0 | 0 |
| D/Y | rs747206654 |
-0.063 | 0.997 | N | 0.637 | 0.49 | 0.666639349654 | gnomAD-2.1.1 | 8.05E-06 | None | None | None | None | N | None | 6.49E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 1.65948E-04 |
| D/Y | rs747206654 |
-0.063 | 0.997 | N | 0.637 | 0.49 | 0.666639349654 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| D/Y | rs747206654 |
-0.063 | 0.997 | N | 0.637 | 0.49 | 0.666639349654 | gnomAD-4.0.0 | 1.8595E-06 | None | None | None | None | N | None | 2.67087E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.60159E-05 |
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 | 0.3955 | ambiguous | 0.3727 | ambiguous | -0.502 | Destabilizing | 0.698 | D | 0.537 | neutral | N | 0.484248211 | None | None | N |
| D/C | 0.7834 | likely_pathogenic | 0.7673 | pathogenic | -0.195 | Destabilizing | 0.998 | D | 0.675 | neutral | None | None | None | None | N |
| D/E | 0.2687 | likely_benign | 0.2656 | benign | -0.388 | Destabilizing | 0.058 | N | 0.374 | neutral | N | 0.472434152 | None | None | N |
| D/F | 0.8408 | likely_pathogenic | 0.8344 | pathogenic | -0.147 | Destabilizing | 0.998 | D | 0.641 | neutral | None | None | None | None | N |
| D/G | 0.1708 | likely_benign | 0.1614 | benign | -0.783 | Destabilizing | 0.006 | N | 0.354 | neutral | N | 0.464974959 | None | None | N |
| D/H | 0.6363 | likely_pathogenic | 0.6308 | pathogenic | -0.189 | Destabilizing | 0.997 | D | 0.5 | neutral | N | 0.5209637 | None | None | N |
| D/I | 0.8081 | likely_pathogenic | 0.7989 | pathogenic | 0.216 | Stabilizing | 0.993 | D | 0.653 | neutral | None | None | None | None | N |
| D/K | 0.722 | likely_pathogenic | 0.7212 | pathogenic | -0.141 | Destabilizing | 0.956 | D | 0.453 | neutral | None | None | None | None | N |
| D/L | 0.7248 | likely_pathogenic | 0.7197 | pathogenic | 0.216 | Stabilizing | 0.978 | D | 0.65 | neutral | None | None | None | None | N |
| D/M | 0.8547 | likely_pathogenic | 0.8438 | pathogenic | 0.445 | Stabilizing | 0.998 | D | 0.659 | neutral | None | None | None | None | N |
| D/N | 0.1471 | likely_benign | 0.1396 | benign | -0.531 | Destabilizing | 0.822 | D | 0.477 | neutral | N | 0.454006593 | None | None | N |
| D/P | 0.9747 | likely_pathogenic | 0.9727 | pathogenic | None | Stabilizing | 0.993 | D | 0.505 | neutral | None | None | None | None | N |
| D/Q | 0.5967 | likely_pathogenic | 0.5869 | pathogenic | -0.427 | Destabilizing | 0.956 | D | 0.459 | neutral | None | None | None | None | N |
| D/R | 0.7388 | likely_pathogenic | 0.7349 | pathogenic | 0.111 | Stabilizing | 0.956 | D | 0.586 | neutral | None | None | None | None | N |
| D/S | 0.2984 | likely_benign | 0.2794 | benign | -0.699 | Destabilizing | 0.86 | D | 0.483 | neutral | None | None | None | None | N |
| D/T | 0.7035 | likely_pathogenic | 0.6833 | pathogenic | -0.475 | Destabilizing | 0.978 | D | 0.468 | neutral | None | None | None | None | N |
| D/V | 0.6059 | likely_pathogenic | 0.6019 | pathogenic | None | Stabilizing | 0.971 | D | 0.65 | neutral | N | 0.489123283 | None | None | N |
| D/W | 0.9496 | likely_pathogenic | 0.9478 | pathogenic | 0.059 | Stabilizing | 0.998 | D | 0.685 | prob.neutral | None | None | None | None | N |
| D/Y | 0.424 | ambiguous | 0.4296 | ambiguous | 0.089 | Stabilizing | 0.997 | D | 0.637 | neutral | N | 0.5096963 | 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.