Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28807 | 86644;86645;86646 | chr2:178559713;178559712;178559711 | chr2:179424440;179424439;179424438 |
| N2AB | 27166 | 81721;81722;81723 | chr2:178559713;178559712;178559711 | chr2:179424440;179424439;179424438 |
| N2A | 26239 | 78940;78941;78942 | chr2:178559713;178559712;178559711 | chr2:179424440;179424439;179424438 |
| N2B | 19742 | 59449;59450;59451 | chr2:178559713;178559712;178559711 | chr2:179424440;179424439;179424438 |
| Novex-1 | 19867 | 59824;59825;59826 | chr2:178559713;178559712;178559711 | chr2:179424440;179424439;179424438 |
| Novex-2 | 19934 | 60025;60026;60027 | chr2:178559713;178559712;178559711 | chr2:179424440;179424439;179424438 |
| 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/C | rs765632053  |
-1.311 | 0.001 | N | 0.325 | 0.167 | 0.363158594168 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.07555E-04 | 0 |
| R/H | rs375800916 |
-1.794 | 0.001 | N | 0.271 | 0.054 | None | gnomAD-2.1.1 | 5.18E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 5.15E-05 | None | 0 | None | 0 | 1.04736E-04 | 0 |
| R/H | rs375800916 |
-1.794 | 0.001 | N | 0.271 | 0.054 | None | gnomAD-3.1.2 | 4.6E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.02908E-04 | 0 | 0 |
| R/H | rs375800916 |
-1.794 | 0.001 | N | 0.271 | 0.054 | None | gnomAD-4.0.0 | 2.12098E-04 | None | None | None | None | I | None | 1.33854E-05 | 1.68509E-05 | None | 3.48165E-05 | 0 | None | 0 | 0 | 2.82754E-04 | 0 | 8.07024E-05 |
| R/L | None | None | 0.03 | N | 0.431 | 0.109 | 0.265929055128 | gnomAD-4.0.0 | 6.89223E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.04041E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.2825 | likely_benign | 0.3195 | benign | -1.363 | Destabilizing | 0.007 | N | 0.342 | neutral | None | None | None | None | I |
| R/C | 0.0857 | likely_benign | 0.103 | benign | -1.406 | Destabilizing | 0.001 | N | 0.325 | neutral | N | 0.491655639 | None | None | I |
| R/D | 0.5331 | ambiguous | 0.5889 | pathogenic | -0.578 | Destabilizing | 0.072 | N | 0.555 | neutral | None | None | None | None | I |
| R/E | 0.2746 | likely_benign | 0.298 | benign | -0.495 | Destabilizing | 0.016 | N | 0.34 | neutral | None | None | None | None | I |
| R/F | 0.2849 | likely_benign | 0.3211 | benign | -1.513 | Destabilizing | None | N | 0.32 | neutral | None | None | None | None | I |
| R/G | 0.1813 | likely_benign | 0.2069 | benign | -1.608 | Destabilizing | 0.058 | N | 0.485 | neutral | N | 0.4405921 | None | None | I |
| R/H | 0.072 | likely_benign | 0.0785 | benign | -1.655 | Destabilizing | 0.001 | N | 0.271 | neutral | N | 0.455137478 | None | None | I |
| R/I | 0.2052 | likely_benign | 0.2213 | benign | -0.707 | Destabilizing | 0.038 | N | 0.571 | neutral | None | None | None | None | I |
| R/K | 0.101 | likely_benign | 0.1034 | benign | -1.417 | Destabilizing | 0.016 | N | 0.341 | neutral | None | None | None | None | I |
| R/L | 0.1895 | likely_benign | 0.2156 | benign | -0.707 | Destabilizing | 0.03 | N | 0.431 | neutral | N | 0.450115661 | None | None | I |
| R/M | 0.1991 | likely_benign | 0.2094 | benign | -0.742 | Destabilizing | 0.356 | N | 0.499 | neutral | None | None | None | None | I |
| R/N | 0.3823 | ambiguous | 0.4362 | ambiguous | -0.767 | Destabilizing | 0.038 | N | 0.351 | neutral | None | None | None | None | I |
| R/P | 0.8973 | likely_pathogenic | 0.9175 | pathogenic | -0.909 | Destabilizing | 0.515 | D | 0.54 | neutral | D | 0.528480444 | None | None | I |
| R/Q | 0.0815 | likely_benign | 0.0859 | benign | -1.135 | Destabilizing | None | N | 0.271 | neutral | None | None | None | None | I |
| R/S | 0.2768 | likely_benign | 0.3152 | benign | -1.655 | Destabilizing | 0.006 | N | 0.247 | neutral | N | 0.410114478 | None | None | I |
| R/T | 0.1696 | likely_benign | 0.1878 | benign | -1.418 | Destabilizing | 0.016 | N | 0.462 | neutral | None | None | None | None | I |
| R/V | 0.2411 | likely_benign | 0.2661 | benign | -0.909 | Destabilizing | 0.072 | N | 0.539 | neutral | None | None | None | None | I |
| R/W | 0.1333 | likely_benign | 0.1463 | benign | -1.107 | Destabilizing | 0.864 | D | 0.493 | neutral | None | None | None | None | I |
| R/Y | 0.1872 | likely_benign | 0.2178 | benign | -0.802 | Destabilizing | 0.038 | N | 0.541 | neutral | None | None | None | None | I |
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.