Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24855 | 74788;74789;74790 | chr2:178571569;178571568;178571567 | chr2:179436296;179436295;179436294 |
| N2AB | 23214 | 69865;69866;69867 | chr2:178571569;178571568;178571567 | chr2:179436296;179436295;179436294 |
| N2A | 22287 | 67084;67085;67086 | chr2:178571569;178571568;178571567 | chr2:179436296;179436295;179436294 |
| N2B | 15790 | 47593;47594;47595 | chr2:178571569;178571568;178571567 | chr2:179436296;179436295;179436294 |
| Novex-1 | 15915 | 47968;47969;47970 | chr2:178571569;178571568;178571567 | chr2:179436296;179436295;179436294 |
| Novex-2 | 15982 | 48169;48170;48171 | chr2:178571569;178571568;178571567 | chr2:179436296;179436295;179436294 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/I | rs759432194  |
-0.06 | None | N | 0.218 | 0.097 | 0.219573609325 | gnomAD-2.1.1 | 1.11296E-04 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 2.80134E-04 | 1.81259E-04 | 1.41084E-04 |
| T/I | rs759432194 |
-0.06 | None | N | 0.218 | 0.097 | 0.219573609325 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 4.41E-05 | 0 | 0 |
| T/I | rs759432194 |
-0.06 | None | N | 0.218 | 0.097 | 0.219573609325 | gnomAD-4.0.0 | 4.2775E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.40757E-04 | 0 | 5.08659E-05 | 0 | 0 |
| T/S | None | None | 0.001 | N | 0.139 | 0.028 | 0.0716867268079 | gnomAD-4.0.0 | 1.59247E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.7852E-05 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.0675 | likely_benign | 0.0646 | benign | -0.452 | Destabilizing | None | N | 0.118 | neutral | N | 0.440788809 | None | None | N |
| T/C | 0.3595 | ambiguous | 0.3264 | benign | -0.292 | Destabilizing | 0.676 | D | 0.237 | neutral | None | None | None | None | N |
| T/D | 0.3542 | ambiguous | 0.2866 | benign | 0.1 | Stabilizing | 0.038 | N | 0.259 | neutral | None | None | None | None | N |
| T/E | 0.3166 | likely_benign | 0.2689 | benign | 0.035 | Stabilizing | 0.072 | N | 0.269 | neutral | None | None | None | None | N |
| T/F | 0.2601 | likely_benign | 0.2135 | benign | -0.841 | Destabilizing | 0.214 | N | 0.315 | neutral | None | None | None | None | N |
| T/G | 0.2054 | likely_benign | 0.1816 | benign | -0.606 | Destabilizing | 0.016 | N | 0.271 | neutral | None | None | None | None | N |
| T/H | 0.2698 | likely_benign | 0.2373 | benign | -0.813 | Destabilizing | 0.356 | N | 0.292 | neutral | None | None | None | None | N |
| T/I | 0.1356 | likely_benign | 0.1039 | benign | -0.159 | Destabilizing | None | N | 0.218 | neutral | N | 0.503146777 | None | None | N |
| T/K | 0.3193 | likely_benign | 0.2756 | benign | -0.479 | Destabilizing | 0.072 | N | 0.269 | neutral | None | None | None | None | N |
| T/L | 0.0916 | likely_benign | 0.0818 | benign | -0.159 | Destabilizing | 0.006 | N | 0.307 | neutral | None | None | None | None | N |
| T/M | 0.0958 | likely_benign | 0.0861 | benign | -0.036 | Destabilizing | 0.214 | N | 0.238 | neutral | None | None | None | None | N |
| T/N | 0.0911 | likely_benign | 0.0836 | benign | -0.225 | Destabilizing | None | N | 0.097 | neutral | N | 0.429206379 | None | None | N |
| T/P | 0.4313 | ambiguous | 0.378 | ambiguous | -0.227 | Destabilizing | 0.171 | N | 0.286 | neutral | N | 0.493025784 | None | None | N |
| T/Q | 0.2454 | likely_benign | 0.2212 | benign | -0.442 | Destabilizing | 0.214 | N | 0.29 | neutral | None | None | None | None | N |
| T/R | 0.298 | likely_benign | 0.2533 | benign | -0.157 | Destabilizing | 0.072 | N | 0.322 | neutral | None | None | None | None | N |
| T/S | 0.0869 | likely_benign | 0.0808 | benign | -0.451 | Destabilizing | 0.001 | N | 0.139 | neutral | N | 0.465991111 | None | None | N |
| T/V | 0.095 | likely_benign | 0.0785 | benign | -0.227 | Destabilizing | 0.006 | N | 0.237 | neutral | None | None | None | None | N |
| T/W | 0.6931 | likely_pathogenic | 0.617 | pathogenic | -0.836 | Destabilizing | 0.864 | D | 0.34 | neutral | None | None | None | None | N |
| T/Y | 0.3057 | likely_benign | 0.2703 | benign | -0.575 | Destabilizing | 0.356 | N | 0.311 | 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.