Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19968 | 60127;60128;60129 | chr2:178592002;178592001;178592000 | chr2:179456729;179456728;179456727 |
| N2AB | 18327 | 55204;55205;55206 | chr2:178592002;178592001;178592000 | chr2:179456729;179456728;179456727 |
| N2A | 17400 | 52423;52424;52425 | chr2:178592002;178592001;178592000 | chr2:179456729;179456728;179456727 |
| N2B | 10903 | 32932;32933;32934 | chr2:178592002;178592001;178592000 | chr2:179456729;179456728;179456727 |
| Novex-1 | 11028 | 33307;33308;33309 | chr2:178592002;178592001;178592000 | chr2:179456729;179456728;179456727 |
| Novex-2 | 11095 | 33508;33509;33510 | chr2:178592002;178592001;178592000 | chr2:179456729;179456728;179456727 |
| 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/R | None | None | 0.974 | N | 0.669 | 0.378 | 0.432266382184 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.66327E-05 |
| P/T | rs758407490  |
-1.26 | 0.842 | N | 0.579 | 0.3 | 0.322510055762 | gnomAD-2.1.1 | 8.07E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.78E-05 | 0 |
| P/T | rs758407490 |
-1.26 | 0.842 | N | 0.579 | 0.3 | 0.322510055762 | gnomAD-4.0.0 | 3.42279E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.59878E-06 | 0 | 1.6575E-05 |
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 | 0.0896 | likely_benign | 0.0803 | benign | -1.024 | Destabilizing | 0.029 | N | 0.202 | neutral | N | 0.482606507 | None | None | N |
| P/C | 0.6807 | likely_pathogenic | 0.618 | pathogenic | -0.754 | Destabilizing | 0.998 | D | 0.683 | prob.neutral | None | None | None | None | N |
| P/D | 0.8234 | likely_pathogenic | 0.7512 | pathogenic | -0.827 | Destabilizing | 0.876 | D | 0.577 | neutral | None | None | None | None | N |
| P/E | 0.613 | likely_pathogenic | 0.5029 | ambiguous | -0.87 | Destabilizing | 0.876 | D | 0.587 | neutral | None | None | None | None | N |
| P/F | 0.7675 | likely_pathogenic | 0.6964 | pathogenic | -0.838 | Destabilizing | 0.049 | N | 0.485 | neutral | None | None | None | None | N |
| P/G | 0.4317 | ambiguous | 0.3734 | ambiguous | -1.276 | Destabilizing | 0.594 | D | 0.593 | neutral | None | None | None | None | N |
| P/H | 0.5119 | ambiguous | 0.4329 | ambiguous | -0.762 | Destabilizing | 0.998 | D | 0.631 | neutral | None | None | None | None | N |
| P/I | 0.5318 | ambiguous | 0.446 | ambiguous | -0.459 | Destabilizing | 0.961 | D | 0.729 | deleterious | None | None | None | None | N |
| P/K | 0.7359 | likely_pathogenic | 0.6264 | pathogenic | -0.98 | Destabilizing | 0.876 | D | 0.585 | neutral | None | None | None | None | N |
| P/L | 0.3313 | likely_benign | 0.2585 | benign | -0.459 | Destabilizing | 0.728 | D | 0.634 | neutral | N | 0.508562616 | None | None | N |
| P/M | 0.5397 | ambiguous | 0.4446 | ambiguous | -0.421 | Destabilizing | 0.994 | D | 0.634 | neutral | None | None | None | None | N |
| P/N | 0.6492 | likely_pathogenic | 0.5611 | ambiguous | -0.727 | Destabilizing | 0.961 | D | 0.673 | prob.neutral | None | None | None | None | N |
| P/Q | 0.4379 | ambiguous | 0.3428 | ambiguous | -0.919 | Destabilizing | 0.974 | D | 0.587 | neutral | N | 0.492486277 | None | None | N |
| P/R | 0.587 | likely_pathogenic | 0.4747 | ambiguous | -0.423 | Destabilizing | 0.974 | D | 0.669 | prob.neutral | N | 0.492232788 | None | None | N |
| P/S | 0.2487 | likely_benign | 0.2116 | benign | -1.168 | Destabilizing | 0.172 | N | 0.283 | neutral | N | 0.510083553 | None | None | N |
| P/T | 0.2434 | likely_benign | 0.1939 | benign | -1.104 | Destabilizing | 0.842 | D | 0.579 | neutral | N | 0.486952869 | None | None | N |
| P/V | 0.3428 | ambiguous | 0.2799 | benign | -0.611 | Destabilizing | 0.876 | D | 0.655 | prob.neutral | None | None | None | None | N |
| P/W | 0.878 | likely_pathogenic | 0.831 | pathogenic | -0.985 | Destabilizing | 0.998 | D | 0.706 | prob.delet. | None | None | None | None | N |
| P/Y | 0.7167 | likely_pathogenic | 0.6465 | pathogenic | -0.702 | Destabilizing | 0.925 | D | 0.718 | prob.delet. | 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.