Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24835 | 74728;74729;74730 | chr2:178571629;178571628;178571627 | chr2:179436356;179436355;179436354 |
| N2AB | 23194 | 69805;69806;69807 | chr2:178571629;178571628;178571627 | chr2:179436356;179436355;179436354 |
| N2A | 22267 | 67024;67025;67026 | chr2:178571629;178571628;178571627 | chr2:179436356;179436355;179436354 |
| N2B | 15770 | 47533;47534;47535 | chr2:178571629;178571628;178571627 | chr2:179436356;179436355;179436354 |
| Novex-1 | 15895 | 47908;47909;47910 | chr2:178571629;178571628;178571627 | chr2:179436356;179436355;179436354 |
| Novex-2 | 15962 | 48109;48110;48111 | chr2:178571629;178571628;178571627 | chr2:179436356;179436355;179436354 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/C | rs201724962  |
0.326 | 0.999 | N | 0.652 | 0.542 | None | gnomAD-2.1.1 | 6.87E-05 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 1.19808E-03 | 0 | None | 0 | None | 0 | 1.79E-05 | 3.33E-04 |
| Y/C | rs201724962 |
0.326 | 0.999 | N | 0.652 | 0.542 | None | gnomAD-3.1.2 | 5.92E-05 | None | None | None | None | N | None | 0 | 1.31079E-04 | 0 | 1.1534E-03 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 9.5511E-04 |
| Y/C | rs201724962 |
0.326 | 0.999 | N | 0.652 | 0.542 | None | gnomAD-4.0.0 | 3.84324E-05 | None | None | None | None | N | None | 0 | 6.67156E-05 | None | 1.18275E-03 | 0 | None | 0 | 0 | 9.32537E-06 | 0 | 1.92197E-04 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/A | 0.8192 | likely_pathogenic | 0.8282 | pathogenic | -0.81 | Destabilizing | 0.916 | D | 0.495 | neutral | None | None | None | None | N |
| Y/C | 0.5052 | ambiguous | 0.5388 | ambiguous | 0.062 | Stabilizing | 0.999 | D | 0.652 | neutral | N | 0.484985907 | None | None | N |
| Y/D | 0.3047 | likely_benign | 0.2984 | benign | 0.957 | Stabilizing | 0.025 | N | 0.484 | neutral | N | 0.420445249 | None | None | N |
| Y/E | 0.7712 | likely_pathogenic | 0.7754 | pathogenic | 0.941 | Stabilizing | 0.845 | D | 0.493 | neutral | None | None | None | None | N |
| Y/F | 0.1708 | likely_benign | 0.1752 | benign | -0.417 | Destabilizing | 0.981 | D | 0.539 | neutral | N | 0.485344876 | None | None | N |
| Y/G | 0.7468 | likely_pathogenic | 0.751 | pathogenic | -1.001 | Destabilizing | 0.975 | D | 0.522 | neutral | None | None | None | None | N |
| Y/H | 0.4938 | ambiguous | 0.5328 | ambiguous | 0.148 | Stabilizing | 0.994 | D | 0.581 | neutral | N | 0.51460899 | None | None | N |
| Y/I | 0.7845 | likely_pathogenic | 0.78 | pathogenic | -0.328 | Destabilizing | 0.987 | D | 0.575 | neutral | None | None | None | None | N |
| Y/K | 0.9026 | likely_pathogenic | 0.9096 | pathogenic | 0.157 | Stabilizing | 0.975 | D | 0.603 | neutral | None | None | None | None | N |
| Y/L | 0.7182 | likely_pathogenic | 0.7299 | pathogenic | -0.328 | Destabilizing | 0.957 | D | 0.563 | neutral | None | None | None | None | N |
| Y/M | 0.7978 | likely_pathogenic | 0.7918 | pathogenic | -0.111 | Destabilizing | 0.999 | D | 0.565 | neutral | None | None | None | None | N |
| Y/N | 0.2431 | likely_benign | 0.2423 | benign | -0.018 | Destabilizing | 0.935 | D | 0.608 | neutral | N | 0.472895654 | None | None | N |
| Y/P | 0.9835 | likely_pathogenic | 0.9845 | pathogenic | -0.469 | Destabilizing | 0.987 | D | 0.657 | neutral | None | None | None | None | N |
| Y/Q | 0.8307 | likely_pathogenic | 0.8472 | pathogenic | 0.008 | Stabilizing | 0.987 | D | 0.571 | neutral | None | None | None | None | N |
| Y/R | 0.8425 | likely_pathogenic | 0.8573 | pathogenic | 0.46 | Stabilizing | 0.987 | D | 0.611 | neutral | None | None | None | None | N |
| Y/S | 0.5089 | ambiguous | 0.5228 | ambiguous | -0.499 | Destabilizing | 0.967 | D | 0.469 | neutral | N | 0.496599233 | None | None | N |
| Y/T | 0.7399 | likely_pathogenic | 0.7401 | pathogenic | -0.426 | Destabilizing | 0.975 | D | 0.563 | neutral | None | None | None | None | N |
| Y/V | 0.6962 | likely_pathogenic | 0.701 | pathogenic | -0.469 | Destabilizing | 0.987 | D | 0.515 | neutral | None | None | None | None | N |
| Y/W | 0.6496 | likely_pathogenic | 0.6585 | pathogenic | -0.494 | Destabilizing | 0.999 | D | 0.559 | 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.