Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27171 | 81736;81737;81738 | chr2:178564621;178564620;178564619 | chr2:179429348;179429347;179429346 |
| N2AB | 25530 | 76813;76814;76815 | chr2:178564621;178564620;178564619 | chr2:179429348;179429347;179429346 |
| N2A | 24603 | 74032;74033;74034 | chr2:178564621;178564620;178564619 | chr2:179429348;179429347;179429346 |
| N2B | 18106 | 54541;54542;54543 | chr2:178564621;178564620;178564619 | chr2:179429348;179429347;179429346 |
| Novex-1 | 18231 | 54916;54917;54918 | chr2:178564621;178564620;178564619 | chr2:179429348;179429347;179429346 |
| Novex-2 | 18298 | 55117;55118;55119 | chr2:178564621;178564620;178564619 | chr2:179429348;179429347;179429346 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| C/R | rs727504678  |
-0.116 | 0.015 | N | 0.651 | 0.405 | 0.516884031612 | gnomAD-2.1.1 | 1.61E-05 | None | None | None | None | N | None | 0 | 5.8E-05 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 8.9E-06 | 0 |
| C/R | rs727504678 |
-0.116 | 0.015 | N | 0.651 | 0.405 | 0.516884031612 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| C/R | rs727504678 |
-0.116 | 0.015 | N | 0.651 | 0.405 | 0.516884031612 | gnomAD-4.0.0 | 7.43746E-06 | None | None | None | None | N | None | 0 | 6.67045E-05 | None | 0 | 0 | None | 0 | 0 | 5.08603E-06 | 2.19597E-05 | 0 |
| C/Y | None | None | 0.979 | N | 0.658 | 0.411 | 0.480349945188 | gnomAD-4.0.0 | 1.59192E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85904E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| C/A | 0.7715 | likely_pathogenic | 0.7535 | pathogenic | -0.887 | Destabilizing | 0.54 | D | 0.614 | neutral | None | None | None | None | N |
| C/D | 0.9956 | likely_pathogenic | 0.9948 | pathogenic | -1.725 | Destabilizing | 0.953 | D | 0.799 | deleterious | None | None | None | None | N |
| C/E | 0.9966 | likely_pathogenic | 0.9964 | pathogenic | -1.602 | Destabilizing | 0.909 | D | 0.755 | deleterious | None | None | None | None | N |
| C/F | 0.8169 | likely_pathogenic | 0.7961 | pathogenic | -0.819 | Destabilizing | 0.979 | D | 0.648 | neutral | N | 0.493060282 | None | None | N |
| C/G | 0.7745 | likely_pathogenic | 0.7491 | pathogenic | -1.138 | Destabilizing | 0.883 | D | 0.76 | deleterious | N | 0.482326107 | None | None | N |
| C/H | 0.9897 | likely_pathogenic | 0.9877 | pathogenic | -1.761 | Destabilizing | 0.987 | D | 0.786 | deleterious | None | None | None | None | N |
| C/I | 0.5468 | ambiguous | 0.5576 | ambiguous | -0.269 | Destabilizing | 0.953 | D | 0.633 | neutral | None | None | None | None | N |
| C/K | 0.9975 | likely_pathogenic | 0.9971 | pathogenic | -0.815 | Destabilizing | 0.587 | D | 0.731 | deleterious | None | None | None | None | N |
| C/L | 0.7361 | likely_pathogenic | 0.7522 | pathogenic | -0.269 | Destabilizing | 0.74 | D | 0.631 | neutral | None | None | None | None | N |
| C/M | 0.8574 | likely_pathogenic | 0.8732 | pathogenic | 0.534 | Stabilizing | 0.996 | D | 0.663 | prob.neutral | None | None | None | None | N |
| C/N | 0.9673 | likely_pathogenic | 0.9674 | pathogenic | -1.175 | Destabilizing | 0.909 | D | 0.794 | deleterious | None | None | None | None | N |
| C/P | 0.9372 | likely_pathogenic | 0.9178 | pathogenic | -0.45 | Destabilizing | 0.984 | D | 0.781 | deleterious | None | None | None | None | N |
| C/Q | 0.9888 | likely_pathogenic | 0.9883 | pathogenic | -1.047 | Destabilizing | 0.909 | D | 0.785 | deleterious | None | None | None | None | N |
| C/R | 0.9796 | likely_pathogenic | 0.9753 | pathogenic | -1.02 | Destabilizing | 0.015 | N | 0.651 | prob.neutral | N | 0.482326107 | None | None | N |
| C/S | 0.7963 | likely_pathogenic | 0.776 | pathogenic | -1.268 | Destabilizing | 0.682 | D | 0.645 | neutral | N | 0.470551728 | None | None | N |
| C/T | 0.7977 | likely_pathogenic | 0.7944 | pathogenic | -1.009 | Destabilizing | 0.74 | D | 0.635 | neutral | None | None | None | None | N |
| C/V | 0.4278 | ambiguous | 0.436 | ambiguous | -0.45 | Destabilizing | 0.852 | D | 0.635 | neutral | None | None | None | None | N |
| C/W | 0.9762 | likely_pathogenic | 0.97 | pathogenic | -1.286 | Destabilizing | 0.994 | D | 0.678 | prob.neutral | N | 0.471058707 | None | None | N |
| C/Y | 0.9509 | likely_pathogenic | 0.9402 | pathogenic | -0.933 | Destabilizing | 0.979 | D | 0.658 | prob.neutral | N | 0.520265526 | 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.