Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28243 | 84952;84953;84954 | chr2:178561405;178561404;178561403 | chr2:179426132;179426131;179426130 |
| N2AB | 26602 | 80029;80030;80031 | chr2:178561405;178561404;178561403 | chr2:179426132;179426131;179426130 |
| N2A | 25675 | 77248;77249;77250 | chr2:178561405;178561404;178561403 | chr2:179426132;179426131;179426130 |
| N2B | 19178 | 57757;57758;57759 | chr2:178561405;178561404;178561403 | chr2:179426132;179426131;179426130 |
| Novex-1 | 19303 | 58132;58133;58134 | chr2:178561405;178561404;178561403 | chr2:179426132;179426131;179426130 |
| Novex-2 | 19370 | 58333;58334;58335 | chr2:178561405;178561404;178561403 | chr2:179426132;179426131;179426130 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/F | rs746193654  |
-0.915 | 0.162 | N | 0.586 | 0.179 | 0.424549175451 | gnomAD-2.1.1 | 8.05E-06 | None | None | None | None | I | None | 0 | 5.79E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| S/F | rs746193654 |
-0.915 | 0.162 | N | 0.586 | 0.179 | 0.424549175451 | gnomAD-4.0.0 | 2.05265E-06 | None | None | None | None | I | None | 0 | 4.47207E-05 | None | 0 | 0 | None | 0 | 0 | 8.99465E-07 | 0 | 0 |
| S/T | None | None | 0.006 | N | 0.334 | 0.06 | 0.0482279557977 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | I | None | 6.33473E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/Y | None | None | 0.162 | N | 0.569 | 0.182 | 0.426551566703 | gnomAD-4.0.0 | 6.84218E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99465E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.0511 | likely_benign | 0.0524 | benign | -0.797 | Destabilizing | None | N | 0.161 | neutral | N | 0.353281681 | None | None | I |
| S/C | 0.0952 | likely_benign | 0.0905 | benign | -0.54 | Destabilizing | 0.162 | N | 0.369 | neutral | N | 0.458718422 | None | None | I |
| S/D | 0.6223 | likely_pathogenic | 0.5687 | pathogenic | -0.599 | Destabilizing | 0.035 | N | 0.301 | neutral | None | None | None | None | I |
| S/E | 0.6304 | likely_pathogenic | 0.5857 | pathogenic | -0.589 | Destabilizing | 0.015 | N | 0.279 | neutral | None | None | None | None | I |
| S/F | 0.2502 | likely_benign | 0.2183 | benign | -0.837 | Destabilizing | 0.162 | N | 0.586 | neutral | N | 0.491694845 | None | None | I |
| S/G | 0.1003 | likely_benign | 0.0946 | benign | -1.069 | Destabilizing | 0.007 | N | 0.323 | neutral | None | None | None | None | I |
| S/H | 0.4555 | ambiguous | 0.4022 | ambiguous | -1.536 | Destabilizing | 0.439 | N | 0.371 | neutral | None | None | None | None | I |
| S/I | 0.1373 | likely_benign | 0.1214 | benign | -0.173 | Destabilizing | 0.018 | N | 0.484 | neutral | None | None | None | None | I |
| S/K | 0.7859 | likely_pathogenic | 0.7288 | pathogenic | -0.93 | Destabilizing | 0.015 | N | 0.291 | neutral | None | None | None | None | I |
| S/L | 0.1052 | likely_benign | 0.0967 | benign | -0.173 | Destabilizing | 0.007 | N | 0.375 | neutral | None | None | None | None | I |
| S/M | 0.1937 | likely_benign | 0.1805 | benign | 0.118 | Stabilizing | 0.204 | N | 0.355 | neutral | None | None | None | None | I |
| S/N | 0.1702 | likely_benign | 0.1443 | benign | -0.876 | Destabilizing | 0.068 | N | 0.291 | neutral | None | None | None | None | I |
| S/P | 0.0644 | likely_benign | 0.0638 | benign | -0.347 | Destabilizing | None | N | 0.251 | neutral | N | 0.325593647 | None | None | I |
| S/Q | 0.53 | ambiguous | 0.4727 | ambiguous | -1.011 | Destabilizing | 0.068 | N | 0.342 | neutral | None | None | None | None | I |
| S/R | 0.7334 | likely_pathogenic | 0.6691 | pathogenic | -0.815 | Destabilizing | 0.035 | N | 0.447 | neutral | None | None | None | None | I |
| S/T | 0.0838 | likely_benign | 0.0821 | benign | -0.845 | Destabilizing | 0.006 | N | 0.334 | neutral | N | 0.41890924 | None | None | I |
| S/V | 0.1255 | likely_benign | 0.1184 | benign | -0.347 | Destabilizing | None | N | 0.407 | neutral | None | None | None | None | I |
| S/W | 0.4633 | ambiguous | 0.3979 | ambiguous | -0.833 | Destabilizing | 0.747 | D | 0.65 | prob.neutral | None | None | None | None | I |
| S/Y | 0.242 | likely_benign | 0.2114 | benign | -0.591 | Destabilizing | 0.162 | N | 0.569 | neutral | N | 0.491868204 | 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.