Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23562 | 70909;70910;70911 | chr2:178575448;178575447;178575446 | chr2:179440175;179440174;179440173 |
| N2AB | 21921 | 65986;65987;65988 | chr2:178575448;178575447;178575446 | chr2:179440175;179440174;179440173 |
| N2A | 20994 | 63205;63206;63207 | chr2:178575448;178575447;178575446 | chr2:179440175;179440174;179440173 |
| N2B | 14497 | 43714;43715;43716 | chr2:178575448;178575447;178575446 | chr2:179440175;179440174;179440173 |
| Novex-1 | 14622 | 44089;44090;44091 | chr2:178575448;178575447;178575446 | chr2:179440175;179440174;179440173 |
| Novex-2 | 14689 | 44290;44291;44292 | chr2:178575448;178575447;178575446 | chr2:179440175;179440174;179440173 |
| 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/I | rs761119454  |
-0.271 | 1.0 | N | 0.804 | 0.494 | 0.495172024023 | gnomAD-2.1.1 | 8.06E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.78E-05 | 0 |
| S/I | rs761119454 |
-0.271 | 1.0 | N | 0.804 | 0.494 | 0.495172024023 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| S/I | rs761119454 |
-0.271 | 1.0 | N | 0.804 | 0.494 | 0.495172024023 | gnomAD-4.0.0 | 1.54948E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.03455E-05 | 1.09806E-05 | 0 |
| S/N | None | None | 0.997 | N | 0.709 | 0.264 | 0.283761946502 | gnomAD-4.0.0 | 6.84312E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99591E-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 | 0.1862 | likely_benign | 0.1792 | benign | -0.486 | Destabilizing | 0.997 | D | 0.593 | neutral | None | None | None | None | I |
| S/C | 0.1683 | likely_benign | 0.1811 | benign | -0.218 | Destabilizing | 1.0 | D | 0.764 | deleterious | N | 0.490148284 | None | None | I |
| S/D | 0.8799 | likely_pathogenic | 0.8982 | pathogenic | -0.095 | Destabilizing | 1.0 | D | 0.727 | prob.delet. | None | None | None | None | I |
| S/E | 0.8997 | likely_pathogenic | 0.9229 | pathogenic | -0.186 | Destabilizing | 1.0 | D | 0.698 | prob.neutral | None | None | None | None | I |
| S/F | 0.6563 | likely_pathogenic | 0.6749 | pathogenic | -1.085 | Destabilizing | 1.0 | D | 0.819 | deleterious | None | None | None | None | I |
| S/G | 0.2881 | likely_benign | 0.2691 | benign | -0.606 | Destabilizing | 1.0 | D | 0.571 | neutral | N | 0.47262887 | None | None | I |
| S/H | 0.7799 | likely_pathogenic | 0.8064 | pathogenic | -1.182 | Destabilizing | 1.0 | D | 0.771 | deleterious | None | None | None | None | I |
| S/I | 0.7414 | likely_pathogenic | 0.7807 | pathogenic | -0.295 | Destabilizing | 1.0 | D | 0.804 | deleterious | N | 0.516695555 | None | None | I |
| S/K | 0.9722 | likely_pathogenic | 0.9786 | pathogenic | -0.487 | Destabilizing | 1.0 | D | 0.716 | prob.delet. | None | None | None | None | I |
| S/L | 0.3074 | likely_benign | 0.3304 | benign | -0.295 | Destabilizing | 1.0 | D | 0.773 | deleterious | None | None | None | None | I |
| S/M | 0.4715 | ambiguous | 0.5203 | ambiguous | 0.163 | Stabilizing | 1.0 | D | 0.771 | deleterious | None | None | None | None | I |
| S/N | 0.5163 | ambiguous | 0.5239 | ambiguous | -0.21 | Destabilizing | 0.997 | D | 0.709 | prob.delet. | N | 0.496451706 | None | None | I |
| S/P | 0.9912 | likely_pathogenic | 0.9912 | pathogenic | -0.331 | Destabilizing | 1.0 | D | 0.752 | deleterious | None | None | None | None | I |
| S/Q | 0.8361 | likely_pathogenic | 0.8577 | pathogenic | -0.529 | Destabilizing | 1.0 | D | 0.767 | deleterious | None | None | None | None | I |
| S/R | 0.9533 | likely_pathogenic | 0.9607 | pathogenic | -0.251 | Destabilizing | 1.0 | D | 0.749 | deleterious | N | 0.48405499 | None | None | I |
| S/T | 0.2103 | likely_benign | 0.2444 | benign | -0.316 | Destabilizing | 0.981 | D | 0.584 | neutral | N | 0.472991854 | None | None | I |
| S/V | 0.6163 | likely_pathogenic | 0.664 | pathogenic | -0.331 | Destabilizing | 1.0 | D | 0.805 | deleterious | None | None | None | None | I |
| S/W | 0.793 | likely_pathogenic | 0.8226 | pathogenic | -1.056 | Destabilizing | 1.0 | D | 0.843 | deleterious | None | None | None | None | I |
| S/Y | 0.6378 | likely_pathogenic | 0.6608 | pathogenic | -0.784 | Destabilizing | 1.0 | D | 0.829 | deleterious | None | None | 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.