Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 35142 | 105649;105650;105651 | chr2:178531191;178531190;178531189 | chr2:179395918;179395917;179395916 |
| N2AB | 33501 | 100726;100727;100728 | chr2:178531191;178531190;178531189 | chr2:179395918;179395917;179395916 |
| N2A | 32574 | 97945;97946;97947 | chr2:178531191;178531190;178531189 | chr2:179395918;179395917;179395916 |
| N2B | 26077 | 78454;78455;78456 | chr2:178531191;178531190;178531189 | chr2:179395918;179395917;179395916 |
| Novex-1 | 26202 | 78829;78830;78831 | chr2:178531191;178531190;178531189 | chr2:179395918;179395917;179395916 |
| Novex-2 | 26269 | 79030;79031;79032 | chr2:178531191;178531190;178531189 | chr2:179395918;179395917;179395916 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| E/K | rs765274398  |
-0.016 | 1.0 | N | 0.601 | 0.405 | 0.304435445954 | gnomAD-2.1.1 | 3.21E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 6.54E-05 | None | 0 | 5.32E-05 | 0 |
| E/K | rs765274398 |
-0.016 | 1.0 | N | 0.601 | 0.405 | 0.304435445954 | gnomAD-3.1.2 | 4.6E-05 | None | None | None | None | N | None | 1.20662E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| E/K | rs765274398 |
-0.016 | 1.0 | N | 0.601 | 0.405 | 0.304435445954 | gnomAD-4.0.0 | 2.41656E-05 | None | None | None | None | N | None | 8.00897E-05 | 0 | None | 0 | 0 | None | 0 | 1.64366E-04 | 2.3731E-05 | 3.29345E-05 | 1.60092E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| E/A | 0.233 | likely_benign | 0.3142 | benign | -0.682 | Destabilizing | 0.999 | D | 0.591 | neutral | N | 0.409822823 | None | None | N |
| E/C | 0.9576 | likely_pathogenic | 0.9724 | pathogenic | -0.253 | Destabilizing | 1.0 | D | 0.731 | prob.delet. | None | None | None | None | N |
| E/D | 0.4201 | ambiguous | 0.5552 | ambiguous | -0.69 | Destabilizing | 0.999 | D | 0.447 | neutral | N | 0.507333514 | None | None | N |
| E/F | 0.9371 | likely_pathogenic | 0.9692 | pathogenic | -0.306 | Destabilizing | 1.0 | D | 0.689 | prob.neutral | None | None | None | None | N |
| E/G | 0.3662 | ambiguous | 0.5003 | ambiguous | -0.963 | Destabilizing | 1.0 | D | 0.618 | neutral | N | 0.506111447 | None | None | N |
| E/H | 0.7645 | likely_pathogenic | 0.8474 | pathogenic | -0.305 | Destabilizing | 1.0 | D | 0.643 | neutral | None | None | None | None | N |
| E/I | 0.6373 | likely_pathogenic | 0.7397 | pathogenic | 0.056 | Stabilizing | 1.0 | D | 0.718 | prob.delet. | None | None | None | None | N |
| E/K | 0.2161 | likely_benign | 0.3 | benign | -0.048 | Destabilizing | 1.0 | D | 0.601 | neutral | N | 0.516163642 | None | None | N |
| E/L | 0.6636 | likely_pathogenic | 0.7803 | pathogenic | 0.056 | Stabilizing | 1.0 | D | 0.694 | prob.neutral | None | None | None | None | N |
| E/M | 0.7099 | likely_pathogenic | 0.8029 | pathogenic | 0.293 | Stabilizing | 1.0 | D | 0.653 | neutral | None | None | None | None | N |
| E/N | 0.6137 | likely_pathogenic | 0.7453 | pathogenic | -0.524 | Destabilizing | 1.0 | D | 0.687 | prob.neutral | None | None | None | None | N |
| E/P | 0.7611 | likely_pathogenic | 0.8309 | pathogenic | -0.169 | Destabilizing | 1.0 | D | 0.627 | neutral | None | None | None | None | N |
| E/Q | 0.2191 | likely_benign | 0.2612 | benign | -0.447 | Destabilizing | 1.0 | D | 0.615 | neutral | N | 0.457621579 | None | None | N |
| E/R | 0.3889 | ambiguous | 0.4775 | ambiguous | 0.212 | Stabilizing | 1.0 | D | 0.677 | prob.neutral | None | None | None | None | N |
| E/S | 0.3872 | ambiguous | 0.5134 | ambiguous | -0.719 | Destabilizing | 0.999 | D | 0.649 | neutral | None | None | None | None | N |
| E/T | 0.4375 | ambiguous | 0.5638 | ambiguous | -0.486 | Destabilizing | 1.0 | D | 0.645 | neutral | None | None | None | None | N |
| E/V | 0.4169 | ambiguous | 0.5202 | ambiguous | -0.169 | Destabilizing | 1.0 | D | 0.682 | prob.neutral | N | 0.487859532 | None | None | N |
| E/W | 0.9775 | likely_pathogenic | 0.988 | pathogenic | -0.058 | Destabilizing | 1.0 | D | 0.733 | prob.delet. | None | None | None | None | N |
| E/Y | 0.8871 | likely_pathogenic | 0.9416 | pathogenic | -0.046 | Destabilizing | 1.0 | D | 0.676 | prob.neutral | 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.