Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32553 | 97882;97883;97884 | chr2:178541420;178541419;178541418 | chr2:179406147;179406146;179406145 |
| N2AB | 30912 | 92959;92960;92961 | chr2:178541420;178541419;178541418 | chr2:179406147;179406146;179406145 |
| N2A | 29985 | 90178;90179;90180 | chr2:178541420;178541419;178541418 | chr2:179406147;179406146;179406145 |
| N2B | 23488 | 70687;70688;70689 | chr2:178541420;178541419;178541418 | chr2:179406147;179406146;179406145 |
| Novex-1 | 23613 | 71062;71063;71064 | chr2:178541420;178541419;178541418 | chr2:179406147;179406146;179406145 |
| Novex-2 | 23680 | 71263;71264;71265 | chr2:178541420;178541419;178541418 | chr2:179406147;179406146;179406145 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/L | rs765136667  |
-0.308 | 0.761 | N | 0.668 | 0.288 | None | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 0 | 5.81E-05 | None | 0 | 0 | None | 0 | None | 0 | 8.89E-06 | 0 |
| P/L | rs765136667 |
-0.308 | 0.761 | N | 0.668 | 0.288 | None | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 7.24E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| P/L | rs765136667 |
-0.308 | 0.761 | N | 0.668 | 0.288 | None | gnomAD-4.0.0 | 4.95916E-06 | None | None | None | None | N | None | 5.34145E-05 | 3.33533E-05 | None | 0 | 0 | None | 0 | 0 | 1.6956E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.1497 | likely_benign | 0.1693 | benign | -1.034 | Destabilizing | 0.006 | N | 0.301 | neutral | N | 0.468949248 | None | None | N |
| P/C | 0.7536 | likely_pathogenic | 0.7707 | pathogenic | -0.726 | Destabilizing | 0.985 | D | 0.726 | prob.delet. | None | None | None | None | N |
| P/D | 0.9134 | likely_pathogenic | 0.9322 | pathogenic | -0.513 | Destabilizing | 0.945 | D | 0.685 | prob.neutral | None | None | None | None | N |
| P/E | 0.7667 | likely_pathogenic | 0.8023 | pathogenic | -0.555 | Destabilizing | 0.894 | D | 0.624 | neutral | None | None | None | None | N |
| P/F | 0.7963 | likely_pathogenic | 0.8231 | pathogenic | -0.857 | Destabilizing | 0.809 | D | 0.759 | deleterious | None | None | None | None | N |
| P/G | 0.7194 | likely_pathogenic | 0.7582 | pathogenic | -1.296 | Destabilizing | 0.547 | D | 0.587 | neutral | None | None | None | None | N |
| P/H | 0.6234 | likely_pathogenic | 0.6807 | pathogenic | -0.828 | Destabilizing | 0.96 | D | 0.693 | prob.neutral | N | 0.489841888 | None | None | N |
| P/I | 0.4982 | ambiguous | 0.5315 | ambiguous | -0.449 | Destabilizing | 0.894 | D | 0.757 | deleterious | None | None | None | None | N |
| P/K | 0.847 | likely_pathogenic | 0.8722 | pathogenic | -0.803 | Destabilizing | 0.894 | D | 0.613 | neutral | None | None | None | None | N |
| P/L | 0.1845 | likely_benign | 0.2198 | benign | -0.449 | Destabilizing | 0.761 | D | 0.668 | neutral | N | 0.514113132 | None | None | N |
| P/M | 0.5025 | ambiguous | 0.533 | ambiguous | -0.352 | Destabilizing | 0.985 | D | 0.674 | neutral | None | None | None | None | N |
| P/N | 0.7633 | likely_pathogenic | 0.8093 | pathogenic | -0.542 | Destabilizing | 0.945 | D | 0.727 | prob.delet. | None | None | None | None | N |
| P/Q | 0.5325 | ambiguous | 0.593 | pathogenic | -0.727 | Destabilizing | 0.945 | D | 0.688 | prob.neutral | None | None | None | None | N |
| P/R | 0.6693 | likely_pathogenic | 0.7125 | pathogenic | -0.317 | Destabilizing | 0.864 | D | 0.727 | prob.delet. | N | 0.470453277 | None | None | N |
| P/S | 0.3586 | ambiguous | 0.4186 | ambiguous | -1.064 | Destabilizing | 0.477 | N | 0.585 | neutral | N | 0.499951756 | None | None | N |
| P/T | 0.2725 | likely_benign | 0.3152 | benign | -0.996 | Destabilizing | 0.864 | D | 0.616 | neutral | N | 0.467698708 | None | None | N |
| P/V | 0.3569 | ambiguous | 0.3789 | ambiguous | -0.607 | Destabilizing | 0.809 | D | 0.629 | neutral | None | None | None | None | N |
| P/W | 0.8998 | likely_pathogenic | 0.9142 | pathogenic | -0.992 | Destabilizing | 0.995 | D | 0.737 | prob.delet. | None | None | None | None | N |
| P/Y | 0.801 | likely_pathogenic | 0.8311 | pathogenic | -0.696 | Destabilizing | 0.07 | N | 0.438 | 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.