Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25480 | 76663;76664;76665 | chr2:178569694;178569693;178569692 | chr2:179434421;179434420;179434419 |
| N2AB | 23839 | 71740;71741;71742 | chr2:178569694;178569693;178569692 | chr2:179434421;179434420;179434419 |
| N2A | 22912 | 68959;68960;68961 | chr2:178569694;178569693;178569692 | chr2:179434421;179434420;179434419 |
| N2B | 16415 | 49468;49469;49470 | chr2:178569694;178569693;178569692 | chr2:179434421;179434420;179434419 |
| Novex-1 | 16540 | 49843;49844;49845 | chr2:178569694;178569693;178569692 | chr2:179434421;179434420;179434419 |
| Novex-2 | 16607 | 50044;50045;50046 | chr2:178569694;178569693;178569692 | chr2:179434421;179434420;179434419 |
| 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 | rs766977350  |
-1.252 | 1.0 | D | 0.823 | 0.52 | 0.724858809077 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 0 | 5.82E-05 | None | 0 | 0 | None | 0 | None | 0 | 8.93E-06 | 0 |
| R/C | rs766977350 |
-1.252 | 1.0 | D | 0.823 | 0.52 | 0.724858809077 | gnomAD-4.0.0 | 1.16377E-05 | None | None | None | None | N | None | 0 | 2.23934E-05 | None | 0 | 0 | None | 0 | 0 | 1.34951E-05 | 1.16004E-05 | 0 |
| R/H | rs759416649 |
-1.799 | 1.0 | D | 0.795 | 0.527 | 0.400899426204 | gnomAD-2.1.1 | 4.66E-05 | None | None | None | None | N | None | 4.14E-05 | 1.98841E-04 | None | 0 | 1.03756E-04 | None | 0 | None | 0 | 7.86E-06 | 2.82805E-04 |
| R/H | rs759416649 |
-1.799 | 1.0 | D | 0.795 | 0.527 | 0.400899426204 | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | N | None | 2.41E-05 | 6.56E-05 | 0 | 2.88018E-04 | 1.93723E-04 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/H | rs759416649 |
-1.799 | 1.0 | D | 0.795 | 0.527 | 0.400899426204 | gnomAD-4.0.0 | 1.67413E-05 | None | None | None | None | N | None | 2.6708E-05 | 1.50265E-04 | None | 3.38043E-05 | 6.71411E-05 | None | 0 | 0 | 8.47847E-06 | 0 | 3.20554E-05 |
| R/P | None | None | 1.0 | D | 0.817 | 0.504 | 0.534335327796 |
Rees (2021)
| None |
CNM 
|
comp het with R14679* | None | None | N | Genetic analysis of TTN in 30 CM patients; comp het with truncating; Protein unfolded | None | None | None | None | None | None | None | None | None | None | None |
| R/P | None | None | 1.0 | D | 0.817 | 0.504 | 0.534335327796 | gnomAD-4.0.0 | 2.73837E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.59882E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.9714 | likely_pathogenic | 0.9642 | pathogenic | -1.436 | Destabilizing | 0.999 | D | 0.599 | neutral | None | None | None | None | N |
| R/C | 0.5504 | ambiguous | 0.5022 | ambiguous | -1.385 | Destabilizing | 1.0 | D | 0.823 | deleterious | D | 0.537119398 | None | None | N |
| R/D | 0.9956 | likely_pathogenic | 0.9954 | pathogenic | -0.888 | Destabilizing | 1.0 | D | 0.8 | deleterious | None | None | None | None | N |
| R/E | 0.9421 | likely_pathogenic | 0.9332 | pathogenic | -0.671 | Destabilizing | 0.999 | D | 0.653 | neutral | None | None | None | None | N |
| R/F | 0.9848 | likely_pathogenic | 0.9812 | pathogenic | -0.496 | Destabilizing | 1.0 | D | 0.861 | deleterious | None | None | None | None | N |
| R/G | 0.9632 | likely_pathogenic | 0.9546 | pathogenic | -1.804 | Destabilizing | 1.0 | D | 0.717 | prob.delet. | D | 0.536612419 | None | None | N |
| R/H | 0.331 | likely_benign | 0.3311 | benign | -1.628 | Destabilizing | 1.0 | D | 0.795 | deleterious | D | 0.536612419 | None | None | N |
| R/I | 0.9316 | likely_pathogenic | 0.9166 | pathogenic | -0.378 | Destabilizing | 1.0 | D | 0.851 | deleterious | None | None | None | None | N |
| R/K | 0.4275 | ambiguous | 0.4131 | ambiguous | -1.033 | Destabilizing | 0.998 | D | 0.622 | neutral | None | None | None | None | N |
| R/L | 0.9114 | likely_pathogenic | 0.8875 | pathogenic | -0.378 | Destabilizing | 1.0 | D | 0.717 | prob.delet. | N | 0.505884411 | None | None | N |
| R/M | 0.9451 | likely_pathogenic | 0.9324 | pathogenic | -0.864 | Destabilizing | 1.0 | D | 0.805 | deleterious | None | None | None | None | N |
| R/N | 0.9751 | likely_pathogenic | 0.9762 | pathogenic | -1.176 | Destabilizing | 1.0 | D | 0.759 | deleterious | None | None | None | None | N |
| R/P | 0.9992 | likely_pathogenic | 0.9986 | pathogenic | -0.717 | Destabilizing | 1.0 | D | 0.817 | deleterious | D | 0.536865909 | None | None | N |
| R/Q | 0.3143 | likely_benign | 0.2683 | benign | -0.93 | Destabilizing | 1.0 | D | 0.764 | deleterious | None | None | None | None | N |
| R/S | 0.9678 | likely_pathogenic | 0.9639 | pathogenic | -1.879 | Destabilizing | 1.0 | D | 0.712 | prob.delet. | N | 0.508086457 | None | None | N |
| R/T | 0.9546 | likely_pathogenic | 0.9486 | pathogenic | -1.453 | Destabilizing | 1.0 | D | 0.718 | prob.delet. | None | None | None | None | N |
| R/V | 0.9474 | likely_pathogenic | 0.9334 | pathogenic | -0.717 | Destabilizing | 1.0 | D | 0.823 | deleterious | None | None | None | None | N |
| R/W | 0.8131 | likely_pathogenic | 0.7773 | pathogenic | -0.153 | Destabilizing | 1.0 | D | 0.807 | deleterious | None | None | None | None | N |
| R/Y | 0.9412 | likely_pathogenic | 0.932 | pathogenic | 0.02 | Stabilizing | 1.0 | D | 0.842 | 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.