Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30436 | 91531;91532;91533 | chr2:178551225;178551224;178551223 | chr2:179415952;179415951;179415950 |
| N2AB | 28795 | 86608;86609;86610 | chr2:178551225;178551224;178551223 | chr2:179415952;179415951;179415950 |
| N2A | 27868 | 83827;83828;83829 | chr2:178551225;178551224;178551223 | chr2:179415952;179415951;179415950 |
| N2B | 21371 | 64336;64337;64338 | chr2:178551225;178551224;178551223 | chr2:179415952;179415951;179415950 |
| Novex-1 | 21496 | 64711;64712;64713 | chr2:178551225;178551224;178551223 | chr2:179415952;179415951;179415950 |
| Novex-2 | 21563 | 64912;64913;64914 | chr2:178551225;178551224;178551223 | chr2:179415952;179415951;179415950 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/G | None | None | 1.0 | N | 0.676 | 0.349 | 0.445210270852 | gnomAD-4.0.0 | 1.36891E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 1.73551E-04 | 8.99586E-07 | 0 | 0 |
| R/L | rs770081431  |
-0.43 | 1.0 | N | 0.676 | 0.499 | 0.649506424125 | 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 |
| R/L | rs770081431 |
-0.43 | 1.0 | N | 0.676 | 0.499 | 0.649506424125 | gnomAD-4.0.0 | 6.84457E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.15969E-05 | 0 |
| R/Q | rs770081431 |
-1.06 | 1.0 | N | 0.731 | 0.295 | 0.223847106136 | gnomAD-2.1.1 | 1.43E-05 | None | None | None | None | N | None | 4.13E-05 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 1.56E-05 | 0 |
| R/Q | rs770081431 |
-1.06 | 1.0 | N | 0.731 | 0.295 | 0.223847106136 | gnomAD-3.1.2 | 3.95E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 5.88E-05 | 0 | 0 |
| R/Q | rs770081431 |
-1.06 | 1.0 | N | 0.731 | 0.295 | 0.223847106136 | gnomAD-4.0.0 | 2.78976E-05 | None | None | None | None | N | None | 2.67251E-05 | 0 | None | 0 | 0 | None | 1.56976E-05 | 1.64528E-04 | 3.30614E-05 | 2.19645E-05 | 0 |
| R/W | rs773600127 |
-0.831 | 1.0 | N | 0.777 | 0.541 | None | gnomAD-2.1.1 | 1.43E-05 | None | None | None | None | N | None | 0 | 5.66E-05 | None | 0 | 5.13E-05 | None | 0 | None | 0 | 0 | 1.40568E-04 |
| R/W | rs773600127 |
-0.831 | 1.0 | N | 0.777 | 0.541 | None | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 2.42E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| R/W | rs773600127 |
-0.831 | 1.0 | N | 0.777 | 0.541 | None | gnomAD-4.0.0 | 1.3019E-05 | None | None | None | None | N | None | 2.67308E-05 | 5.0025E-05 | None | 0 | 0 | None | 0 | 0 | 1.27159E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.6633 | likely_pathogenic | 0.6559 | pathogenic | -0.15 | Destabilizing | 0.999 | D | 0.548 | neutral | None | None | None | None | N |
| R/C | 0.4296 | ambiguous | 0.4461 | ambiguous | -0.093 | Destabilizing | 1.0 | D | 0.767 | deleterious | None | None | None | None | N |
| R/D | 0.9078 | likely_pathogenic | 0.9015 | pathogenic | 0.023 | Stabilizing | 1.0 | D | 0.75 | deleterious | None | None | None | None | N |
| R/E | 0.6863 | likely_pathogenic | 0.6761 | pathogenic | 0.105 | Stabilizing | 0.999 | D | 0.598 | neutral | None | None | None | None | N |
| R/F | 0.9232 | likely_pathogenic | 0.9281 | pathogenic | -0.23 | Destabilizing | 1.0 | D | 0.754 | deleterious | None | None | None | None | N |
| R/G | 0.4782 | ambiguous | 0.4876 | ambiguous | -0.4 | Destabilizing | 1.0 | D | 0.676 | prob.neutral | N | 0.485617022 | None | None | N |
| R/H | 0.2682 | likely_benign | 0.2815 | benign | -0.869 | Destabilizing | 1.0 | D | 0.727 | prob.delet. | None | None | None | None | N |
| R/I | 0.8123 | likely_pathogenic | 0.8163 | pathogenic | 0.489 | Stabilizing | 1.0 | D | 0.771 | deleterious | None | None | None | None | N |
| R/K | 0.1772 | likely_benign | 0.1766 | benign | -0.155 | Destabilizing | 0.998 | D | 0.438 | neutral | None | None | None | None | N |
| R/L | 0.6633 | likely_pathogenic | 0.6795 | pathogenic | 0.489 | Stabilizing | 1.0 | D | 0.676 | prob.neutral | N | 0.493080664 | None | None | N |
| R/M | 0.7076 | likely_pathogenic | 0.7195 | pathogenic | 0.14 | Stabilizing | 1.0 | D | 0.697 | prob.neutral | None | None | None | None | N |
| R/N | 0.8391 | likely_pathogenic | 0.8364 | pathogenic | 0.286 | Stabilizing | 1.0 | D | 0.73 | prob.delet. | None | None | None | None | N |
| R/P | 0.8011 | likely_pathogenic | 0.7953 | pathogenic | 0.298 | Stabilizing | 1.0 | D | 0.745 | deleterious | N | 0.492734995 | None | None | N |
| R/Q | 0.197 | likely_benign | 0.2014 | benign | 0.117 | Stabilizing | 1.0 | D | 0.731 | prob.delet. | N | 0.517190723 | None | None | N |
| R/S | 0.7291 | likely_pathogenic | 0.7168 | pathogenic | -0.219 | Destabilizing | 1.0 | D | 0.703 | prob.neutral | None | None | None | None | N |
| R/T | 0.6606 | likely_pathogenic | 0.6576 | pathogenic | 0.016 | Stabilizing | 1.0 | D | 0.701 | prob.neutral | None | None | None | None | N |
| R/V | 0.8089 | likely_pathogenic | 0.8087 | pathogenic | 0.298 | Stabilizing | 1.0 | D | 0.741 | deleterious | None | None | None | None | N |
| R/W | 0.5288 | ambiguous | 0.5756 | pathogenic | -0.129 | Destabilizing | 1.0 | D | 0.777 | deleterious | N | 0.493587643 | None | None | N |
| R/Y | 0.7939 | likely_pathogenic | 0.8136 | pathogenic | 0.248 | Stabilizing | 1.0 | D | 0.763 | deleterious | 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.