Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22469 | 67630;67631;67632 | chr2:178579792;178579791;178579790 | chr2:179444519;179444518;179444517 |
| N2AB | 20828 | 62707;62708;62709 | chr2:178579792;178579791;178579790 | chr2:179444519;179444518;179444517 |
| N2A | 19901 | 59926;59927;59928 | chr2:178579792;178579791;178579790 | chr2:179444519;179444518;179444517 |
| N2B | 13404 | 40435;40436;40437 | chr2:178579792;178579791;178579790 | chr2:179444519;179444518;179444517 |
| Novex-1 | 13529 | 40810;40811;40812 | chr2:178579792;178579791;178579790 | chr2:179444519;179444518;179444517 |
| Novex-2 | 13596 | 41011;41012;41013 | chr2:178579792;178579791;178579790 | chr2:179444519;179444518;179444517 |
| 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/R | rs753623758  |
-0.314 | None | N | 0.299 | 0.106 | 0.181679512989 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.96E-06 | 0 |
| S/R | rs753623758 |
-0.314 | None | N | 0.299 | 0.106 | 0.181679512989 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| S/R | rs753623758 |
-0.314 | None | N | 0.299 | 0.106 | 0.181679512989 | gnomAD-4.0.0 | 3.09941E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.39129E-06 | 0 | 1.60149E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.0952 | likely_benign | 0.0947 | benign | -0.787 | Destabilizing | 0.007 | N | 0.314 | neutral | None | None | None | None | N |
| S/C | 0.1063 | likely_benign | 0.0964 | benign | -0.668 | Destabilizing | 0.295 | N | 0.551 | neutral | N | 0.496991596 | None | None | N |
| S/D | 0.341 | ambiguous | 0.2765 | benign | -0.579 | Destabilizing | 0.016 | N | 0.33 | neutral | None | None | None | None | N |
| S/E | 0.4356 | ambiguous | 0.3786 | ambiguous | -0.581 | Destabilizing | 0.016 | N | 0.347 | neutral | None | None | None | None | N |
| S/F | 0.1775 | likely_benign | 0.1614 | benign | -1.116 | Destabilizing | 0.356 | N | 0.602 | neutral | None | None | None | None | N |
| S/G | 0.1415 | likely_benign | 0.1244 | benign | -1.014 | Destabilizing | 0.012 | N | 0.327 | neutral | N | 0.46805433 | None | None | N |
| S/H | 0.2429 | likely_benign | 0.2007 | benign | -1.555 | Destabilizing | 0.214 | N | 0.563 | neutral | None | None | None | None | N |
| S/I | 0.1182 | likely_benign | 0.1093 | benign | -0.288 | Destabilizing | 0.029 | N | 0.495 | neutral | N | 0.446562775 | None | None | N |
| S/K | 0.6534 | likely_pathogenic | 0.5687 | pathogenic | -0.652 | Destabilizing | 0.016 | N | 0.351 | neutral | None | None | None | None | N |
| S/L | 0.1017 | likely_benign | 0.0978 | benign | -0.288 | Destabilizing | 0.016 | N | 0.452 | neutral | None | None | None | None | N |
| S/M | 0.1702 | likely_benign | 0.1604 | benign | 0.067 | Stabilizing | 0.356 | N | 0.561 | neutral | None | None | None | None | N |
| S/N | 0.118 | likely_benign | 0.1014 | benign | -0.694 | Destabilizing | None | N | 0.191 | neutral | N | 0.432556115 | None | None | N |
| S/P | 0.8419 | likely_pathogenic | 0.8332 | pathogenic | -0.422 | Destabilizing | 0.136 | N | 0.537 | neutral | None | None | None | None | N |
| S/Q | 0.4055 | ambiguous | 0.3446 | ambiguous | -0.914 | Destabilizing | 0.072 | N | 0.479 | neutral | None | None | None | None | N |
| S/R | 0.5443 | ambiguous | 0.4685 | ambiguous | -0.536 | Destabilizing | None | N | 0.299 | neutral | N | 0.440924882 | None | None | N |
| S/T | 0.0676 | likely_benign | 0.0712 | benign | -0.692 | Destabilizing | None | N | 0.193 | neutral | N | 0.326964658 | None | None | N |
| S/V | 0.1248 | likely_benign | 0.1166 | benign | -0.422 | Destabilizing | None | N | 0.395 | neutral | None | None | None | None | N |
| S/W | 0.3211 | likely_benign | 0.3026 | benign | -1.074 | Destabilizing | 0.864 | D | 0.615 | neutral | None | None | None | None | N |
| S/Y | 0.1818 | likely_benign | 0.1644 | benign | -0.784 | Destabilizing | 0.356 | N | 0.581 | 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.