Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21091 | 63496;63497;63498 | chr2:178588136;178588135;178588134 | chr2:179452863;179452862;179452861 |
| N2AB | 19450 | 58573;58574;58575 | chr2:178588136;178588135;178588134 | chr2:179452863;179452862;179452861 |
| N2A | 18523 | 55792;55793;55794 | chr2:178588136;178588135;178588134 | chr2:179452863;179452862;179452861 |
| N2B | 12026 | 36301;36302;36303 | chr2:178588136;178588135;178588134 | chr2:179452863;179452862;179452861 |
| Novex-1 | 12151 | 36676;36677;36678 | chr2:178588136;178588135;178588134 | chr2:179452863;179452862;179452861 |
| Novex-2 | 12218 | 36877;36878;36879 | chr2:178588136;178588135;178588134 | chr2:179452863;179452862;179452861 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/E | rs374168580  |
-0.724 | 1.0 | N | 0.424 | 0.365 | 0.359557344763 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| D/E | rs374168580 |
-0.724 | 1.0 | N | 0.424 | 0.365 | 0.359557344763 | gnomAD-4.0.0 | 6.85058E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.16104E-05 | 0 |
| D/V | None | None | 1.0 | N | 0.735 | 0.459 | 0.584827705416 | gnomAD-4.0.0 | 6.85045E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.16101E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.9118 | likely_pathogenic | 0.8418 | pathogenic | -0.666 | Destabilizing | 1.0 | D | 0.729 | prob.delet. | N | 0.49536207 | None | None | I |
| D/C | 0.9785 | likely_pathogenic | 0.9546 | pathogenic | -0.313 | Destabilizing | 1.0 | D | 0.72 | prob.delet. | None | None | None | None | I |
| D/E | 0.8859 | likely_pathogenic | 0.8041 | pathogenic | -0.65 | Destabilizing | 1.0 | D | 0.424 | neutral | N | 0.495500201 | None | None | I |
| D/F | 0.9864 | likely_pathogenic | 0.9786 | pathogenic | -0.246 | Destabilizing | 1.0 | D | 0.721 | prob.delet. | None | None | None | None | I |
| D/G | 0.8882 | likely_pathogenic | 0.8223 | pathogenic | -1.038 | Destabilizing | 1.0 | D | 0.691 | prob.neutral | N | 0.503630956 | None | None | I |
| D/H | 0.9252 | likely_pathogenic | 0.8689 | pathogenic | -0.667 | Destabilizing | 1.0 | D | 0.709 | prob.delet. | N | 0.508795517 | None | None | I |
| D/I | 0.9837 | likely_pathogenic | 0.9638 | pathogenic | 0.327 | Stabilizing | 1.0 | D | 0.729 | prob.delet. | None | None | None | None | I |
| D/K | 0.9794 | likely_pathogenic | 0.9569 | pathogenic | -0.574 | Destabilizing | 1.0 | D | 0.751 | deleterious | None | None | None | None | I |
| D/L | 0.9714 | likely_pathogenic | 0.9505 | pathogenic | 0.327 | Stabilizing | 1.0 | D | 0.732 | prob.delet. | None | None | None | None | I |
| D/M | 0.9914 | likely_pathogenic | 0.9831 | pathogenic | 0.818 | Stabilizing | 1.0 | D | 0.713 | prob.delet. | None | None | None | None | I |
| D/N | 0.3248 | likely_benign | 0.2599 | benign | -0.968 | Destabilizing | 1.0 | D | 0.718 | prob.delet. | N | 0.474055037 | None | None | I |
| D/P | 0.9834 | likely_pathogenic | 0.9694 | pathogenic | 0.021 | Stabilizing | 1.0 | D | 0.77 | deleterious | None | None | None | None | I |
| D/Q | 0.9657 | likely_pathogenic | 0.9255 | pathogenic | -0.801 | Destabilizing | 1.0 | D | 0.788 | deleterious | None | None | None | None | I |
| D/R | 0.9713 | likely_pathogenic | 0.9404 | pathogenic | -0.451 | Destabilizing | 1.0 | D | 0.76 | deleterious | None | None | None | None | I |
| D/S | 0.6144 | likely_pathogenic | 0.4974 | ambiguous | -1.279 | Destabilizing | 1.0 | D | 0.727 | prob.delet. | None | None | None | None | I |
| D/T | 0.8617 | likely_pathogenic | 0.8039 | pathogenic | -0.97 | Destabilizing | 1.0 | D | 0.757 | deleterious | None | None | None | None | I |
| D/V | 0.9542 | likely_pathogenic | 0.912 | pathogenic | 0.021 | Stabilizing | 1.0 | D | 0.735 | prob.delet. | N | 0.5107573 | None | None | I |
| D/W | 0.9958 | likely_pathogenic | 0.9934 | pathogenic | -0.076 | Destabilizing | 1.0 | D | 0.707 | prob.neutral | None | None | None | None | I |
| D/Y | 0.9062 | likely_pathogenic | 0.8444 | pathogenic | -0.015 | Destabilizing | 1.0 | D | 0.703 | prob.neutral | D | 0.541485308 | 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.