Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18609 | 56050;56051;56052 | chr2:178601079;178601078;178601077 | chr2:179465806;179465805;179465804 |
| N2AB | 16968 | 51127;51128;51129 | chr2:178601079;178601078;178601077 | chr2:179465806;179465805;179465804 |
| N2A | 16041 | 48346;48347;48348 | chr2:178601079;178601078;178601077 | chr2:179465806;179465805;179465804 |
| N2B | 9544 | 28855;28856;28857 | chr2:178601079;178601078;178601077 | chr2:179465806;179465805;179465804 |
| Novex-1 | 9669 | 29230;29231;29232 | chr2:178601079;178601078;178601077 | chr2:179465806;179465805;179465804 |
| Novex-2 | 9736 | 29431;29432;29433 | chr2:178601079;178601078;178601077 | chr2:179465806;179465805;179465804 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/F | None | None | 0.879 | N | 0.733 | 0.49 | 0.699564077875 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| S/Y | None | None | 0.957 | N | 0.739 | 0.51 | 0.728295594408 | gnomAD-4.0.0 | 2.40064E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 2.75482E-04 | None | 0 | 0 | 1.3125E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.1149 | likely_benign | 0.0859 | benign | -0.425 | Destabilizing | None | N | 0.305 | neutral | N | 0.449179006 | None | None | I |
| S/C | 0.1528 | likely_benign | 0.131 | benign | -0.222 | Destabilizing | 0.965 | D | 0.646 | neutral | D | 0.526141067 | None | None | I |
| S/D | 0.9019 | likely_pathogenic | 0.929 | pathogenic | -0.508 | Destabilizing | 0.733 | D | 0.666 | neutral | None | None | None | None | I |
| S/E | 0.8915 | likely_pathogenic | 0.9064 | pathogenic | -0.588 | Destabilizing | 0.575 | D | 0.603 | neutral | None | None | None | None | I |
| S/F | 0.5206 | ambiguous | 0.4963 | ambiguous | -0.993 | Destabilizing | 0.879 | D | 0.733 | prob.delet. | N | 0.495250392 | None | None | I |
| S/G | 0.3636 | ambiguous | 0.3684 | ambiguous | -0.565 | Destabilizing | 0.218 | N | 0.552 | neutral | None | None | None | None | I |
| S/H | 0.6855 | likely_pathogenic | 0.7081 | pathogenic | -1.191 | Destabilizing | 0.991 | D | 0.645 | neutral | None | None | None | None | I |
| S/I | 0.6195 | likely_pathogenic | 0.6218 | pathogenic | -0.178 | Destabilizing | 0.826 | D | 0.719 | prob.delet. | None | None | None | None | I |
| S/K | 0.963 | likely_pathogenic | 0.9683 | pathogenic | -0.589 | Destabilizing | 0.575 | D | 0.612 | neutral | None | None | None | None | I |
| S/L | 0.2489 | likely_benign | 0.2119 | benign | -0.178 | Destabilizing | 0.404 | N | 0.666 | neutral | None | None | None | None | I |
| S/M | 0.429 | ambiguous | 0.3902 | ambiguous | 0.337 | Stabilizing | 0.973 | D | 0.647 | neutral | None | None | None | None | I |
| S/N | 0.5405 | ambiguous | 0.6244 | pathogenic | -0.394 | Destabilizing | 0.733 | D | 0.697 | prob.neutral | None | None | None | None | I |
| S/P | 0.9892 | likely_pathogenic | 0.9925 | pathogenic | -0.231 | Destabilizing | 0.879 | D | 0.658 | neutral | N | 0.506353208 | None | None | I |
| S/Q | 0.7965 | likely_pathogenic | 0.801 | pathogenic | -0.736 | Destabilizing | 0.906 | D | 0.658 | neutral | None | None | None | None | I |
| S/R | 0.941 | likely_pathogenic | 0.9404 | pathogenic | -0.319 | Destabilizing | 0.826 | D | 0.656 | neutral | None | None | None | None | I |
| S/T | 0.264 | likely_benign | 0.2713 | benign | -0.424 | Destabilizing | 0.296 | N | 0.586 | neutral | D | 0.522407328 | None | None | I |
| S/V | 0.5137 | ambiguous | 0.4745 | ambiguous | -0.231 | Destabilizing | 0.404 | N | 0.675 | neutral | None | None | None | None | I |
| S/W | 0.7546 | likely_pathogenic | 0.7599 | pathogenic | -0.989 | Destabilizing | 0.991 | D | 0.781 | deleterious | None | None | None | None | I |
| S/Y | 0.4769 | ambiguous | 0.4938 | ambiguous | -0.706 | Destabilizing | 0.957 | D | 0.739 | prob.delet. | N | 0.513101158 | None | None | I |
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.