Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25531 | 76816;76817;76818 | chr2:178569541;178569540;178569539 | chr2:179434268;179434267;179434266 |
| N2AB | 23890 | 71893;71894;71895 | chr2:178569541;178569540;178569539 | chr2:179434268;179434267;179434266 |
| N2A | 22963 | 69112;69113;69114 | chr2:178569541;178569540;178569539 | chr2:179434268;179434267;179434266 |
| N2B | 16466 | 49621;49622;49623 | chr2:178569541;178569540;178569539 | chr2:179434268;179434267;179434266 |
| Novex-1 | 16591 | 49996;49997;49998 | chr2:178569541;178569540;178569539 | chr2:179434268;179434267;179434266 |
| Novex-2 | 16658 | 50197;50198;50199 | chr2:178569541;178569540;178569539 | chr2:179434268;179434267;179434266 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/I | rs878933531  |
None | 0.805 | N | 0.441 | 0.415 | None | gnomAD-4.0.0 | 3.60097E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.9375E-06 | 0 | 0 |
| F/S | rs976954474 |
-1.898 | 0.983 | N | 0.707 | 0.543 | 0.802449804186 | gnomAD-2.1.1 | 7.16E-06 | None | None | None | None | I | None | 8.27E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| F/S | rs976954474 |
-1.898 | 0.983 | N | 0.707 | 0.543 | 0.802449804186 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| F/S | rs976954474 |
-1.898 | 0.983 | N | 0.707 | 0.543 | 0.802449804186 | gnomAD-4.0.0 | 3.10039E-06 | None | None | None | None | I | None | 4.01177E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.69576E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/A | 0.8458 | likely_pathogenic | 0.8745 | pathogenic | -1.727 | Destabilizing | 0.916 | D | 0.581 | neutral | None | None | None | None | I |
| F/C | 0.6172 | likely_pathogenic | 0.7172 | pathogenic | -1.064 | Destabilizing | 0.999 | D | 0.706 | prob.neutral | N | 0.493352559 | None | None | I |
| F/D | 0.9591 | likely_pathogenic | 0.9668 | pathogenic | 0.203 | Stabilizing | 0.996 | D | 0.759 | deleterious | None | None | None | None | I |
| F/E | 0.9654 | likely_pathogenic | 0.9715 | pathogenic | 0.278 | Stabilizing | 0.987 | D | 0.756 | deleterious | None | None | None | None | I |
| F/G | 0.9442 | likely_pathogenic | 0.9549 | pathogenic | -2.016 | Highly Destabilizing | 0.987 | D | 0.735 | prob.delet. | None | None | None | None | I |
| F/H | 0.7104 | likely_pathogenic | 0.7501 | pathogenic | -0.207 | Destabilizing | 0.999 | D | 0.673 | neutral | None | None | None | None | I |
| F/I | 0.5625 | ambiguous | 0.6601 | pathogenic | -0.889 | Destabilizing | 0.805 | D | 0.441 | neutral | N | 0.517049942 | None | None | I |
| F/K | 0.9622 | likely_pathogenic | 0.9659 | pathogenic | -0.892 | Destabilizing | 0.987 | D | 0.754 | deleterious | None | None | None | None | I |
| F/L | 0.9419 | likely_pathogenic | 0.9577 | pathogenic | -0.889 | Destabilizing | 0.025 | N | 0.287 | neutral | N | 0.503331283 | None | None | I |
| F/M | 0.7232 | likely_pathogenic | 0.7567 | pathogenic | -0.814 | Destabilizing | 0.975 | D | 0.59 | neutral | None | None | None | None | I |
| F/N | 0.8474 | likely_pathogenic | 0.8584 | pathogenic | -1.022 | Destabilizing | 0.996 | D | 0.753 | deleterious | None | None | None | None | I |
| F/P | 0.9935 | likely_pathogenic | 0.9948 | pathogenic | -1.158 | Destabilizing | 0.996 | D | 0.739 | prob.delet. | None | None | None | None | I |
| F/Q | 0.8951 | likely_pathogenic | 0.9092 | pathogenic | -0.992 | Destabilizing | 0.996 | D | 0.737 | prob.delet. | None | None | None | None | I |
| F/R | 0.8816 | likely_pathogenic | 0.8937 | pathogenic | -0.356 | Destabilizing | 0.987 | D | 0.759 | deleterious | None | None | None | None | I |
| F/S | 0.7187 | likely_pathogenic | 0.7586 | pathogenic | -1.856 | Destabilizing | 0.983 | D | 0.707 | prob.neutral | N | 0.47527789 | None | None | I |
| F/T | 0.8023 | likely_pathogenic | 0.8338 | pathogenic | -1.685 | Destabilizing | 0.975 | D | 0.677 | prob.neutral | None | None | None | None | I |
| F/V | 0.552 | ambiguous | 0.6462 | pathogenic | -1.158 | Destabilizing | 0.805 | D | 0.512 | neutral | N | 0.516876583 | None | None | I |
| F/W | 0.6771 | likely_pathogenic | 0.719 | pathogenic | -0.124 | Destabilizing | 0.999 | D | 0.564 | neutral | None | None | None | None | I |
| F/Y | 0.2447 | likely_benign | 0.2795 | benign | -0.354 | Destabilizing | 0.944 | D | 0.482 | neutral | D | 0.52459199 | 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.