Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26780 | 80563;80564;80565 | chr2:178565794;178565793;178565792 | chr2:179430521;179430520;179430519 |
| N2AB | 25139 | 75640;75641;75642 | chr2:178565794;178565793;178565792 | chr2:179430521;179430520;179430519 |
| N2A | 24212 | 72859;72860;72861 | chr2:178565794;178565793;178565792 | chr2:179430521;179430520;179430519 |
| N2B | 17715 | 53368;53369;53370 | chr2:178565794;178565793;178565792 | chr2:179430521;179430520;179430519 |
| Novex-1 | 17840 | 53743;53744;53745 | chr2:178565794;178565793;178565792 | chr2:179430521;179430520;179430519 |
| Novex-2 | 17907 | 53944;53945;53946 | chr2:178565794;178565793;178565792 | chr2:179430521;179430520;179430519 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/L | rs771965424  |
-0.229 | 0.961 | N | 0.633 | 0.306 | 0.507928266286 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| P/L | rs771965424 |
-0.229 | 0.961 | N | 0.633 | 0.306 | 0.507928266286 | gnomAD-4.0.0 | 3.18326E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.8592E-06 | 1.43283E-05 | 0 |
| P/S | rs775149188 |
-0.206 | 0.39 | N | 0.281 | 0.255 | 0.233150807113 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | N | None | 1.14758E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| P/T | rs775149188 |
-0.259 | 0.877 | N | 0.686 | 0.324 | 0.328222422547 | gnomAD-2.1.1 | 8.05E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.78E-05 | 0 |
| P/T | rs775149188 |
-0.259 | 0.877 | N | 0.686 | 0.324 | 0.328222422547 | gnomAD-4.0.0 | 4.10566E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.39738E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.0677 | likely_benign | 0.0695 | benign | -0.546 | Destabilizing | 0.022 | N | 0.259 | neutral | N | 0.469600222 | None | None | N |
| P/C | 0.3824 | ambiguous | 0.3788 | ambiguous | -0.608 | Destabilizing | 0.999 | D | 0.769 | deleterious | None | None | None | None | N |
| P/D | 0.7969 | likely_pathogenic | 0.7457 | pathogenic | -0.241 | Destabilizing | 0.971 | D | 0.567 | neutral | None | None | None | None | N |
| P/E | 0.3972 | ambiguous | 0.3729 | ambiguous | -0.363 | Destabilizing | 0.971 | D | 0.577 | neutral | None | None | None | None | N |
| P/F | 0.5543 | ambiguous | 0.4659 | ambiguous | -0.888 | Destabilizing | 0.999 | D | 0.743 | deleterious | None | None | None | None | N |
| P/G | 0.5079 | ambiguous | 0.4612 | ambiguous | -0.667 | Destabilizing | 0.825 | D | 0.561 | neutral | None | None | None | None | N |
| P/H | 0.3563 | ambiguous | 0.2892 | benign | -0.234 | Destabilizing | 0.998 | D | 0.752 | deleterious | N | 0.492520778 | None | None | N |
| P/I | 0.1487 | likely_benign | 0.1432 | benign | -0.38 | Destabilizing | 0.971 | D | 0.825 | deleterious | None | None | None | None | N |
| P/K | 0.3321 | likely_benign | 0.2865 | benign | -0.242 | Destabilizing | 0.971 | D | 0.572 | neutral | None | None | None | None | N |
| P/L | 0.1222 | likely_benign | 0.1045 | benign | -0.38 | Destabilizing | 0.961 | D | 0.633 | neutral | N | 0.469350414 | None | None | N |
| P/M | 0.2165 | likely_benign | 0.2079 | benign | -0.23 | Destabilizing | 0.999 | D | 0.75 | deleterious | None | None | None | None | N |
| P/N | 0.5273 | ambiguous | 0.4737 | ambiguous | -0.002 | Destabilizing | 0.971 | D | 0.845 | deleterious | None | None | None | None | N |
| P/Q | 0.1934 | likely_benign | 0.1732 | benign | -0.307 | Destabilizing | 0.985 | D | 0.536 | neutral | None | None | None | None | N |
| P/R | 0.2442 | likely_benign | 0.2054 | benign | 0.278 | Stabilizing | 0.981 | D | 0.833 | deleterious | N | 0.511435399 | None | None | N |
| P/S | 0.1685 | likely_benign | 0.1601 | benign | -0.409 | Destabilizing | 0.39 | N | 0.281 | neutral | N | 0.48285954 | None | None | N |
| P/T | 0.1104 | likely_benign | 0.1029 | benign | -0.432 | Destabilizing | 0.877 | D | 0.686 | prob.delet. | N | 0.509104096 | None | None | N |
| P/V | 0.0974 | likely_benign | 0.1026 | benign | -0.401 | Destabilizing | 0.943 | D | 0.563 | neutral | None | None | None | None | N |
| P/W | 0.8195 | likely_pathogenic | 0.7523 | pathogenic | -0.92 | Destabilizing | 0.999 | D | 0.739 | deleterious | None | None | None | None | N |
| P/Y | 0.5845 | likely_pathogenic | 0.4977 | ambiguous | -0.59 | Destabilizing | 0.999 | D | 0.742 | 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.