Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30861 | 92806;92807;92808 | chr2:178549045;178549044;178549043 | chr2:179413772;179413771;179413770 |
| N2AB | 29220 | 87883;87884;87885 | chr2:178549045;178549044;178549043 | chr2:179413772;179413771;179413770 |
| N2A | 28293 | 85102;85103;85104 | chr2:178549045;178549044;178549043 | chr2:179413772;179413771;179413770 |
| N2B | 21796 | 65611;65612;65613 | chr2:178549045;178549044;178549043 | chr2:179413772;179413771;179413770 |
| Novex-1 | 21921 | 65986;65987;65988 | chr2:178549045;178549044;178549043 | chr2:179413772;179413771;179413770 |
| Novex-2 | 21988 | 66187;66188;66189 | chr2:178549045;178549044;178549043 | chr2:179413772;179413771;179413770 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| C/F | None | None | 0.949 | N | 0.74 | 0.335 | 0.705029066125 | gnomAD-4.0.0 | 1.36836E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79886E-06 | 0 | 0 |
| C/R | rs2154147860  |
None | 0.901 | N | 0.791 | 0.444 | 0.64097366104 | 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 |
| C/Y | rs1045877862 |
-1.623 | 0.983 | N | 0.745 | 0.344 | 0.735756410601 | gnomAD-2.1.1 | 8.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.78E-05 | 0 |
| C/Y | rs1045877862 |
-1.623 | 0.983 | N | 0.745 | 0.344 | 0.735756410601 | gnomAD-4.0.0 | 3.42089E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.49716E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| C/A | 0.3763 | ambiguous | 0.3559 | ambiguous | -1.646 | Destabilizing | 0.011 | N | 0.335 | neutral | None | None | None | None | N |
| C/D | 0.8239 | likely_pathogenic | 0.8181 | pathogenic | -1.644 | Destabilizing | 0.961 | D | 0.801 | deleterious | None | None | None | None | N |
| C/E | 0.7369 | likely_pathogenic | 0.717 | pathogenic | -1.412 | Destabilizing | 0.923 | D | 0.8 | deleterious | None | None | None | None | N |
| C/F | 0.4502 | ambiguous | 0.4461 | ambiguous | -1.03 | Destabilizing | 0.949 | D | 0.74 | deleterious | N | 0.494025861 | None | None | N |
| C/G | 0.2058 | likely_benign | 0.1995 | benign | -1.975 | Destabilizing | 0.565 | D | 0.749 | deleterious | N | 0.510014034 | None | None | N |
| C/H | 0.5528 | ambiguous | 0.5325 | ambiguous | -2.217 | Highly Destabilizing | 0.996 | D | 0.777 | deleterious | None | None | None | None | N |
| C/I | 0.6816 | likely_pathogenic | 0.6786 | pathogenic | -0.75 | Destabilizing | 0.923 | D | 0.717 | prob.delet. | None | None | None | None | N |
| C/K | 0.5951 | likely_pathogenic | 0.5721 | pathogenic | -1.289 | Destabilizing | 0.923 | D | 0.789 | deleterious | None | None | None | None | N |
| C/L | 0.552 | ambiguous | 0.5421 | ambiguous | -0.75 | Destabilizing | 0.633 | D | 0.629 | neutral | None | None | None | None | N |
| C/M | 0.6271 | likely_pathogenic | 0.6261 | pathogenic | -0.156 | Destabilizing | 0.996 | D | 0.701 | prob.neutral | None | None | None | None | N |
| C/N | 0.549 | ambiguous | 0.556 | ambiguous | -1.836 | Destabilizing | 0.961 | D | 0.801 | deleterious | None | None | None | None | N |
| C/P | 0.9905 | likely_pathogenic | 0.9903 | pathogenic | -1.029 | Destabilizing | 0.961 | D | 0.803 | deleterious | None | None | None | None | N |
| C/Q | 0.3671 | ambiguous | 0.3347 | benign | -1.343 | Destabilizing | 0.961 | D | 0.799 | deleterious | None | None | None | None | N |
| C/R | 0.2643 | likely_benign | 0.2474 | benign | -1.725 | Destabilizing | 0.901 | D | 0.791 | deleterious | N | 0.40192099 | None | None | N |
| C/S | 0.2772 | likely_benign | 0.2765 | benign | -2.11 | Highly Destabilizing | 0.565 | D | 0.643 | neutral | N | 0.456216835 | None | None | N |
| C/T | 0.5069 | ambiguous | 0.5046 | ambiguous | -1.717 | Destabilizing | 0.775 | D | 0.683 | prob.neutral | None | None | None | None | N |
| C/V | 0.5521 | ambiguous | 0.5488 | ambiguous | -1.029 | Destabilizing | 0.633 | D | 0.643 | neutral | None | None | None | None | N |
| C/W | 0.7264 | likely_pathogenic | 0.7268 | pathogenic | -1.502 | Destabilizing | 0.995 | D | 0.738 | prob.delet. | N | 0.509320601 | None | None | N |
| C/Y | 0.4743 | ambiguous | 0.4605 | ambiguous | -1.285 | Destabilizing | 0.983 | D | 0.745 | deleterious | N | 0.496103374 | 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.