Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26982 | 81169;81170;81171 | chr2:178565188;178565187;178565186 | chr2:179429915;179429914;179429913 |
| N2AB | 25341 | 76246;76247;76248 | chr2:178565188;178565187;178565186 | chr2:179429915;179429914;179429913 |
| N2A | 24414 | 73465;73466;73467 | chr2:178565188;178565187;178565186 | chr2:179429915;179429914;179429913 |
| N2B | 17917 | 53974;53975;53976 | chr2:178565188;178565187;178565186 | chr2:179429915;179429914;179429913 |
| Novex-1 | 18042 | 54349;54350;54351 | chr2:178565188;178565187;178565186 | chr2:179429915;179429914;179429913 |
| Novex-2 | 18109 | 54550;54551;54552 | chr2:178565188;178565187;178565186 | chr2:179429915;179429914;179429913 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/I | rs200406978  |
None | 0.003 | N | 0.167 | 0.19 | 0.171388866994 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 6.56E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| F/I | rs200406978 |
None | 0.003 | N | 0.167 | 0.19 | 0.171388866994 | gnomAD-4.0.0 | 1.23966E-06 | None | None | None | None | N | None | 0 | 3.33578E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| F/L | rs200406978 |
-1.212 | 0.063 | N | 0.5 | 0.172 | 0.141422826196 | gnomAD-2.1.1 | 5.40289E-04 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 4.74166E-03 | None | 0 | 3.92E-05 | 1.40607E-04 |
| F/L | rs200406978 |
-1.212 | 0.063 | N | 0.5 | 0.172 | 0.141422826196 | gnomAD-3.1.2 | 1.71008E-04 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 7.36E-05 | 4.14422E-03 | 0 |
| F/L | rs200406978 |
-1.212 | 0.063 | N | 0.5 | 0.172 | 0.141422826196 | 1000 genomes | 1.19808E-03 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 6.1E-03 | None |
| F/L | rs200406978 |
-1.212 | 0.063 | N | 0.5 | 0.172 | 0.141422826196 | gnomAD-4.0.0 | 1.59184E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.8591E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/A | 0.57 | likely_pathogenic | 0.5513 | ambiguous | -2.688 | Highly Destabilizing | 0.742 | D | 0.651 | neutral | None | None | None | None | N |
| F/C | 0.2854 | likely_benign | 0.2414 | benign | -1.918 | Destabilizing | 0.994 | D | 0.697 | prob.neutral | N | 0.503976283 | None | None | N |
| F/D | 0.916 | likely_pathogenic | 0.8977 | pathogenic | -2.306 | Highly Destabilizing | 0.984 | D | 0.801 | deleterious | None | None | None | None | N |
| F/E | 0.8875 | likely_pathogenic | 0.8627 | pathogenic | -2.132 | Highly Destabilizing | 0.984 | D | 0.797 | deleterious | None | None | None | None | N |
| F/G | 0.8544 | likely_pathogenic | 0.8372 | pathogenic | -3.118 | Highly Destabilizing | 0.953 | D | 0.793 | deleterious | None | None | None | None | N |
| F/H | 0.7804 | likely_pathogenic | 0.7295 | pathogenic | -1.442 | Destabilizing | 0.996 | D | 0.693 | prob.neutral | None | None | None | None | N |
| F/I | 0.1135 | likely_benign | 0.1047 | benign | -1.326 | Destabilizing | 0.003 | N | 0.167 | neutral | N | 0.410601975 | None | None | N |
| F/K | 0.9007 | likely_pathogenic | 0.8769 | pathogenic | -2.122 | Highly Destabilizing | 0.953 | D | 0.8 | deleterious | None | None | None | None | N |
| F/L | 0.6483 | likely_pathogenic | 0.597 | pathogenic | -1.326 | Destabilizing | 0.063 | N | 0.5 | neutral | N | 0.456835697 | None | None | N |
| F/M | 0.2839 | likely_benign | 0.2618 | benign | -1.078 | Destabilizing | 0.91 | D | 0.672 | neutral | None | None | None | None | N |
| F/N | 0.7812 | likely_pathogenic | 0.7482 | pathogenic | -2.447 | Highly Destabilizing | 0.984 | D | 0.798 | deleterious | None | None | None | None | N |
| F/P | 0.9115 | likely_pathogenic | 0.8901 | pathogenic | -1.785 | Destabilizing | 0.984 | D | 0.781 | deleterious | None | None | None | None | N |
| F/Q | 0.8426 | likely_pathogenic | 0.8045 | pathogenic | -2.414 | Highly Destabilizing | 0.984 | D | 0.784 | deleterious | None | None | None | None | N |
| F/R | 0.8478 | likely_pathogenic | 0.8241 | pathogenic | -1.526 | Destabilizing | 0.984 | D | 0.794 | deleterious | None | None | None | None | N |
| F/S | 0.5794 | likely_pathogenic | 0.5575 | ambiguous | -3.217 | Highly Destabilizing | 0.815 | D | 0.761 | deleterious | N | 0.470536318 | None | None | N |
| F/T | 0.4666 | ambiguous | 0.4551 | ambiguous | -2.931 | Highly Destabilizing | 0.742 | D | 0.739 | prob.delet. | None | None | None | None | N |
| F/V | 0.151 | likely_benign | 0.1397 | benign | -1.785 | Destabilizing | 0.063 | N | 0.551 | neutral | N | 0.394013583 | None | None | N |
| F/W | 0.4771 | ambiguous | 0.4188 | ambiguous | -0.379 | Destabilizing | 0.996 | D | 0.608 | neutral | None | None | None | None | N |
| F/Y | 0.2631 | likely_benign | 0.2195 | benign | -0.742 | Destabilizing | 0.815 | D | 0.628 | neutral | N | 0.485563881 | 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.