Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25401 | 76426;76427;76428 | chr2:178569931;178569930;178569929 | chr2:179434658;179434657;179434656 |
| N2AB | 23760 | 71503;71504;71505 | chr2:178569931;178569930;178569929 | chr2:179434658;179434657;179434656 |
| N2A | 22833 | 68722;68723;68724 | chr2:178569931;178569930;178569929 | chr2:179434658;179434657;179434656 |
| N2B | 16336 | 49231;49232;49233 | chr2:178569931;178569930;178569929 | chr2:179434658;179434657;179434656 |
| Novex-1 | 16461 | 49606;49607;49608 | chr2:178569931;178569930;178569929 | chr2:179434658;179434657;179434656 |
| Novex-2 | 16528 | 49807;49808;49809 | chr2:178569931;178569930;178569929 | chr2:179434658;179434657;179434656 |
| 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 | None | None | 0.999 | N | 0.469 | 0.108 | 0.208816687407 | gnomAD-4.0.0 | 1.59274E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86049E-06 | 0 | 0 |
| D/V | rs1559385033  |
0.334 | 1.0 | N | 0.759 | 0.596 | 0.376921832658 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.28E-05 | None | 0 | 0 | 0 |
| D/V | rs1559385033 |
0.334 | 1.0 | N | 0.759 | 0.596 | 0.376921832658 | gnomAD-4.0.0 | 3.18564E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.86812E-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 | 0.6843 | likely_pathogenic | 0.7685 | pathogenic | -0.267 | Destabilizing | 1.0 | D | 0.713 | prob.delet. | N | 0.509192023 | None | None | N |
| D/C | 0.9515 | likely_pathogenic | 0.9685 | pathogenic | 0.003 | Stabilizing | 1.0 | D | 0.828 | deleterious | None | None | None | None | N |
| D/E | 0.5294 | ambiguous | 0.6488 | pathogenic | -0.352 | Destabilizing | 0.999 | D | 0.469 | neutral | N | 0.481872136 | None | None | N |
| D/F | 0.9285 | likely_pathogenic | 0.9507 | pathogenic | -0.322 | Destabilizing | 1.0 | D | 0.804 | deleterious | None | None | None | None | N |
| D/G | 0.8339 | likely_pathogenic | 0.889 | pathogenic | -0.445 | Destabilizing | 1.0 | D | 0.774 | deleterious | N | 0.512560402 | None | None | N |
| D/H | 0.819 | likely_pathogenic | 0.8583 | pathogenic | -0.15 | Destabilizing | 1.0 | D | 0.879 | deleterious | N | 0.464335714 | None | None | N |
| D/I | 0.8276 | likely_pathogenic | 0.8878 | pathogenic | 0.147 | Stabilizing | 1.0 | D | 0.788 | deleterious | None | None | None | None | N |
| D/K | 0.9041 | likely_pathogenic | 0.9353 | pathogenic | 0.174 | Stabilizing | 1.0 | D | 0.831 | deleterious | None | None | None | None | N |
| D/L | 0.7807 | likely_pathogenic | 0.844 | pathogenic | 0.147 | Stabilizing | 1.0 | D | 0.769 | deleterious | None | None | None | None | N |
| D/M | 0.9397 | likely_pathogenic | 0.96 | pathogenic | 0.263 | Stabilizing | 1.0 | D | 0.799 | deleterious | None | None | None | None | N |
| D/N | 0.319 | likely_benign | 0.372 | ambiguous | 0.009 | Stabilizing | 1.0 | D | 0.773 | deleterious | N | 0.453459934 | None | None | N |
| D/P | 0.9305 | likely_pathogenic | 0.9492 | pathogenic | 0.03 | Stabilizing | 1.0 | D | 0.818 | deleterious | None | None | None | None | N |
| D/Q | 0.8632 | likely_pathogenic | 0.9037 | pathogenic | 0.02 | Stabilizing | 1.0 | D | 0.824 | deleterious | None | None | None | None | N |
| D/R | 0.9118 | likely_pathogenic | 0.9367 | pathogenic | 0.344 | Stabilizing | 1.0 | D | 0.797 | deleterious | None | None | None | None | N |
| D/S | 0.4794 | ambiguous | 0.5367 | ambiguous | -0.116 | Destabilizing | 1.0 | D | 0.78 | deleterious | None | None | None | None | N |
| D/T | 0.7854 | likely_pathogenic | 0.853 | pathogenic | 0.012 | Stabilizing | 1.0 | D | 0.824 | deleterious | None | None | None | None | N |
| D/V | 0.7042 | likely_pathogenic | 0.8092 | pathogenic | 0.03 | Stabilizing | 1.0 | D | 0.759 | deleterious | N | 0.469309236 | None | None | N |
| D/W | 0.9885 | likely_pathogenic | 0.9919 | pathogenic | -0.238 | Destabilizing | 1.0 | D | 0.765 | deleterious | None | None | None | None | N |
| D/Y | 0.6777 | likely_pathogenic | 0.7599 | pathogenic | -0.106 | Destabilizing | 1.0 | D | 0.803 | deleterious | N | 0.470830174 | 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.