Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29947 | 90064;90065;90066 | chr2:178553061;178553060;178553059 | chr2:179417788;179417787;179417786 |
| N2AB | 28306 | 85141;85142;85143 | chr2:178553061;178553060;178553059 | chr2:179417788;179417787;179417786 |
| N2A | 27379 | 82360;82361;82362 | chr2:178553061;178553060;178553059 | chr2:179417788;179417787;179417786 |
| N2B | 20882 | 62869;62870;62871 | chr2:178553061;178553060;178553059 | chr2:179417788;179417787;179417786 |
| Novex-1 | 21007 | 63244;63245;63246 | chr2:178553061;178553060;178553059 | chr2:179417788;179417787;179417786 |
| Novex-2 | 21074 | 63445;63446;63447 | chr2:178553061;178553060;178553059 | chr2:179417788;179417787;179417786 |
| 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/P | None | None | 0.836 | N | 0.709 | 0.221 | 0.132336055621 | gnomAD-4.0.0 | 6.84829E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.997E-07 | 0 | 0 |
| R/Q | rs762912526  |
0.057 | 0.011 | N | 0.307 | 0.113 | None | gnomAD-2.1.1 | 2.43E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 5.35E-05 | 0 |
| R/Q | rs762912526 |
0.057 | 0.011 | N | 0.307 | 0.113 | None | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 4.41E-05 | 0 | 0 |
| R/Q | rs762912526 |
0.057 | 0.011 | N | 0.307 | 0.113 | None | gnomAD-4.0.0 | 1.48849E-05 | None | None | None | None | N | None | 1.33551E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.86519E-05 | 1.09818E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.2865 | likely_benign | 0.2502 | benign | -0.004 | Destabilizing | 0.157 | N | 0.622 | neutral | None | None | None | None | N |
| R/C | 0.1423 | likely_benign | 0.1155 | benign | -0.118 | Destabilizing | 0.968 | D | 0.73 | prob.delet. | None | None | None | None | N |
| R/D | 0.6439 | likely_pathogenic | 0.5873 | pathogenic | -0.158 | Destabilizing | 0.567 | D | 0.649 | neutral | None | None | None | None | N |
| R/E | 0.3242 | likely_benign | 0.2899 | benign | -0.108 | Destabilizing | 0.157 | N | 0.57 | neutral | None | None | None | None | N |
| R/F | 0.495 | ambiguous | 0.4411 | ambiguous | -0.251 | Destabilizing | 0.396 | N | 0.717 | prob.delet. | None | None | None | None | N |
| R/G | 0.2356 | likely_benign | 0.1946 | benign | -0.18 | Destabilizing | 0.417 | N | 0.647 | neutral | N | 0.463798955 | None | None | N |
| R/H | 0.1124 | likely_benign | 0.1032 | benign | -0.642 | Destabilizing | 0.567 | D | 0.543 | neutral | None | None | None | None | N |
| R/I | 0.2607 | likely_benign | 0.2301 | benign | 0.421 | Stabilizing | 0.396 | N | 0.677 | prob.neutral | None | None | None | None | N |
| R/K | 0.0991 | likely_benign | 0.0912 | benign | -0.072 | Destabilizing | 0.072 | N | 0.535 | neutral | None | None | None | None | N |
| R/L | 0.1781 | likely_benign | 0.1627 | benign | 0.421 | Stabilizing | 0.002 | N | 0.399 | neutral | N | 0.483205616 | None | None | N |
| R/M | 0.2734 | likely_benign | 0.2404 | benign | 0.05 | Stabilizing | 0.396 | N | 0.625 | neutral | None | None | None | None | N |
| R/N | 0.4425 | ambiguous | 0.3924 | ambiguous | 0.183 | Stabilizing | 0.567 | D | 0.55 | neutral | None | None | None | None | N |
| R/P | 0.4073 | ambiguous | 0.3799 | ambiguous | 0.299 | Stabilizing | 0.836 | D | 0.709 | prob.delet. | N | 0.491388201 | None | None | N |
| R/Q | 0.085 | likely_benign | 0.1013 | benign | 0.06 | Stabilizing | 0.011 | N | 0.307 | neutral | N | 0.507493804 | None | None | N |
| R/S | 0.4092 | ambiguous | 0.3511 | ambiguous | -0.137 | Destabilizing | 0.157 | N | 0.655 | neutral | None | None | None | None | N |
| R/T | 0.2498 | likely_benign | 0.2171 | benign | 0.035 | Stabilizing | 0.272 | N | 0.645 | neutral | None | None | None | None | N |
| R/V | 0.3068 | likely_benign | 0.2743 | benign | 0.299 | Stabilizing | 0.157 | N | 0.668 | neutral | None | None | None | None | N |
| R/W | 0.2071 | likely_benign | 0.1718 | benign | -0.324 | Destabilizing | 0.968 | D | 0.794 | deleterious | None | None | None | None | N |
| R/Y | 0.3781 | ambiguous | 0.3125 | benign | 0.08 | Stabilizing | 0.726 | D | 0.695 | prob.neutral | 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.