Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 33286 | 100081;100082;100083 | chr2:178537351;178537350;178537349 | chr2:179402078;179402077;179402076 |
| N2AB | 31645 | 95158;95159;95160 | chr2:178537351;178537350;178537349 | chr2:179402078;179402077;179402076 |
| N2A | 30718 | 92377;92378;92379 | chr2:178537351;178537350;178537349 | chr2:179402078;179402077;179402076 |
| N2B | 24221 | 72886;72887;72888 | chr2:178537351;178537350;178537349 | chr2:179402078;179402077;179402076 |
| Novex-1 | 24346 | 73261;73262;73263 | chr2:178537351;178537350;178537349 | chr2:179402078;179402077;179402076 |
| Novex-2 | 24413 | 73462;73463;73464 | chr2:178537351;178537350;178537349 | chr2:179402078;179402077;179402076 |
| 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/D | rs1362585366  |
-1.366 | 0.979 | N | 0.51 | 0.268 | 0.439763647824 | gnomAD-2.1.1 | 5.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.05E-05 | 0 |
| E/K | rs780655169 |
-0.915 | 0.999 | N | 0.659 | 0.33 | None | gnomAD-2.1.1 | 1.5E-05 | None | None | None | None | N | None | 6.95E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.08E-05 | 0 |
| E/K | rs780655169 |
-0.915 | 0.999 | N | 0.659 | 0.33 | None | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| E/K | rs780655169 |
-0.915 | 0.999 | N | 0.659 | 0.33 | None | gnomAD-4.0.0 | 7.75374E-06 | None | None | None | None | N | None | 1.38812E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 7.82733E-06 | 0 | 3.36666E-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 | 0.3079 | likely_benign | 0.3136 | benign | -0.85 | Destabilizing | 0.997 | D | 0.689 | prob.neutral | N | 0.491980926 | None | None | N |
| E/C | 0.9181 | likely_pathogenic | 0.9299 | pathogenic | -0.566 | Destabilizing | 1.0 | D | 0.721 | prob.delet. | None | None | None | None | N |
| E/D | 0.2873 | likely_benign | 0.3394 | benign | -1.301 | Destabilizing | 0.979 | D | 0.51 | neutral | N | 0.493021076 | None | None | N |
| E/F | 0.8622 | likely_pathogenic | 0.8579 | pathogenic | -0.144 | Destabilizing | 1.0 | D | 0.699 | prob.neutral | None | None | None | None | N |
| E/G | 0.5364 | ambiguous | 0.531 | ambiguous | -1.259 | Destabilizing | 1.0 | D | 0.67 | neutral | D | 0.536638567 | None | None | N |
| E/H | 0.6589 | likely_pathogenic | 0.6527 | pathogenic | -0.501 | Destabilizing | 1.0 | D | 0.662 | neutral | None | None | None | None | N |
| E/I | 0.4545 | ambiguous | 0.4742 | ambiguous | 0.28 | Stabilizing | 0.999 | D | 0.719 | prob.delet. | None | None | None | None | N |
| E/K | 0.3231 | likely_benign | 0.3064 | benign | -0.886 | Destabilizing | 0.999 | D | 0.659 | neutral | N | 0.474875245 | None | None | N |
| E/L | 0.631 | likely_pathogenic | 0.6629 | pathogenic | 0.28 | Stabilizing | 0.999 | D | 0.71 | prob.delet. | None | None | None | None | N |
| E/M | 0.6111 | likely_pathogenic | 0.633 | pathogenic | 0.751 | Stabilizing | 0.999 | D | 0.691 | prob.neutral | None | None | None | None | N |
| E/N | 0.4538 | ambiguous | 0.4973 | ambiguous | -1.377 | Destabilizing | 0.999 | D | 0.729 | prob.delet. | None | None | None | None | N |
| E/P | 0.9909 | likely_pathogenic | 0.9862 | pathogenic | -0.075 | Destabilizing | 0.995 | D | 0.705 | prob.neutral | None | None | None | None | N |
| E/Q | 0.2093 | likely_benign | 0.2162 | benign | -1.194 | Destabilizing | 0.999 | D | 0.666 | neutral | N | 0.497213387 | None | None | N |
| E/R | 0.5002 | ambiguous | 0.4653 | ambiguous | -0.58 | Destabilizing | 1.0 | D | 0.72 | prob.delet. | None | None | None | None | N |
| E/S | 0.3859 | ambiguous | 0.4157 | ambiguous | -1.742 | Destabilizing | 0.998 | D | 0.711 | prob.delet. | None | None | None | None | N |
| E/T | 0.3313 | likely_benign | 0.3542 | ambiguous | -1.4 | Destabilizing | 1.0 | D | 0.709 | prob.delet. | None | None | None | None | N |
| E/V | 0.2816 | likely_benign | 0.305 | benign | -0.075 | Destabilizing | 0.999 | D | 0.72 | prob.delet. | N | 0.493194434 | None | None | N |
| E/W | 0.9647 | likely_pathogenic | 0.9637 | pathogenic | 0.09 | Stabilizing | 1.0 | D | 0.723 | prob.delet. | None | None | None | None | N |
| E/Y | 0.8168 | likely_pathogenic | 0.8079 | pathogenic | 0.097 | Stabilizing | 1.0 | D | 0.707 | 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.