Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16869 | 50830;50831;50832 | chr2:178611624;178611623;178611622 | chr2:179476351;179476350;179476349 |
| N2AB | 15228 | 45907;45908;45909 | chr2:178611624;178611623;178611622 | chr2:179476351;179476350;179476349 |
| N2A | 14301 | 43126;43127;43128 | chr2:178611624;178611623;178611622 | chr2:179476351;179476350;179476349 |
| N2B | 7804 | 23635;23636;23637 | chr2:178611624;178611623;178611622 | chr2:179476351;179476350;179476349 |
| Novex-1 | 7929 | 24010;24011;24012 | chr2:178611624;178611623;178611622 | chr2:179476351;179476350;179476349 |
| Novex-2 | 7996 | 24211;24212;24213 | chr2:178611624;178611623;178611622 | chr2:179476351;179476350;179476349 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/F | None | None | 0.959 | N | 0.699 | 0.287 | 0.439018943094 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| I/T | rs184856328  |
-3.186 | 0.979 | D | 0.739 | 0.506 | None | gnomAD-2.1.1 | 7.16E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.57E-05 | 0 |
| I/T | rs184856328 |
-3.186 | 0.979 | D | 0.739 | 0.506 | None | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.95008E-04 | None | 0 | 0 | 1.47E-05 | 2.07125E-04 | 0 |
| I/T | rs184856328 |
-3.186 | 0.979 | D | 0.739 | 0.506 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 1E-03 | 0 | None | None | None | 0 | None |
| I/T | rs184856328 |
-3.186 | 0.979 | D | 0.739 | 0.506 | None | gnomAD-4.0.0 | 6.08997E-06 | None | None | None | None | N | None | 3.48699E-05 | 0 | None | 0 | 1.14338E-04 | None | 0 | 0 | 2.41013E-06 | 4.69836E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.948 | likely_pathogenic | 0.9485 | pathogenic | -3.264 | Highly Destabilizing | 0.927 | D | 0.648 | neutral | None | None | None | None | N |
| I/C | 0.9708 | likely_pathogenic | 0.9773 | pathogenic | -2.629 | Highly Destabilizing | 1.0 | D | 0.743 | deleterious | None | None | None | None | N |
| I/D | 0.9992 | likely_pathogenic | 0.9988 | pathogenic | -3.923 | Highly Destabilizing | 0.999 | D | 0.791 | deleterious | None | None | None | None | N |
| I/E | 0.9977 | likely_pathogenic | 0.9967 | pathogenic | -3.66 | Highly Destabilizing | 0.999 | D | 0.785 | deleterious | None | None | None | None | N |
| I/F | 0.5604 | ambiguous | 0.5709 | pathogenic | -1.995 | Destabilizing | 0.959 | D | 0.699 | prob.neutral | N | 0.478613799 | None | None | N |
| I/G | 0.996 | likely_pathogenic | 0.9953 | pathogenic | -3.848 | Highly Destabilizing | 0.995 | D | 0.783 | deleterious | None | None | None | None | N |
| I/H | 0.9942 | likely_pathogenic | 0.9927 | pathogenic | -3.225 | Highly Destabilizing | 1.0 | D | 0.762 | deleterious | None | None | None | None | N |
| I/K | 0.9933 | likely_pathogenic | 0.989 | pathogenic | -2.806 | Highly Destabilizing | 0.995 | D | 0.787 | deleterious | None | None | None | None | N |
| I/L | 0.2473 | likely_benign | 0.2652 | benign | -1.529 | Destabilizing | 0.01 | N | 0.202 | neutral | N | 0.465616892 | None | None | N |
| I/M | 0.2945 | likely_benign | 0.3025 | benign | -1.466 | Destabilizing | 0.677 | D | 0.449 | neutral | N | 0.480107017 | None | None | N |
| I/N | 0.9891 | likely_pathogenic | 0.9859 | pathogenic | -3.297 | Highly Destabilizing | 0.998 | D | 0.789 | deleterious | D | 0.631417041 | None | None | N |
| I/P | 0.9973 | likely_pathogenic | 0.9955 | pathogenic | -2.095 | Highly Destabilizing | 0.999 | D | 0.789 | deleterious | None | None | None | None | N |
| I/Q | 0.9937 | likely_pathogenic | 0.9912 | pathogenic | -3.114 | Highly Destabilizing | 0.995 | D | 0.789 | deleterious | None | None | None | None | N |
| I/R | 0.988 | likely_pathogenic | 0.983 | pathogenic | -2.416 | Highly Destabilizing | 0.995 | D | 0.791 | deleterious | None | None | None | None | N |
| I/S | 0.9816 | likely_pathogenic | 0.9787 | pathogenic | -3.969 | Highly Destabilizing | 0.979 | D | 0.746 | deleterious | D | 0.576812763 | None | None | N |
| I/T | 0.9326 | likely_pathogenic | 0.9313 | pathogenic | -3.557 | Highly Destabilizing | 0.979 | D | 0.739 | prob.delet. | D | 0.589003278 | None | None | N |
| I/V | 0.1666 | likely_benign | 0.1796 | benign | -2.095 | Highly Destabilizing | 0.677 | D | 0.417 | neutral | N | 0.448445327 | None | None | N |
| I/W | 0.987 | likely_pathogenic | 0.9864 | pathogenic | -2.441 | Highly Destabilizing | 1.0 | D | 0.76 | deleterious | None | None | None | None | N |
| I/Y | 0.9612 | likely_pathogenic | 0.9605 | pathogenic | -2.253 | Highly Destabilizing | 0.999 | D | 0.797 | 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.