Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25022 | 75289;75290;75291 | chr2:178571068;178571067;178571066 | chr2:179435795;179435794;179435793 |
| N2AB | 23381 | 70366;70367;70368 | chr2:178571068;178571067;178571066 | chr2:179435795;179435794;179435793 |
| N2A | 22454 | 67585;67586;67587 | chr2:178571068;178571067;178571066 | chr2:179435795;179435794;179435793 |
| N2B | 15957 | 48094;48095;48096 | chr2:178571068;178571067;178571066 | chr2:179435795;179435794;179435793 |
| Novex-1 | 16082 | 48469;48470;48471 | chr2:178571068;178571067;178571066 | chr2:179435795;179435794;179435793 |
| Novex-2 | 16149 | 48670;48671;48672 | chr2:178571068;178571067;178571066 | chr2:179435795;179435794;179435793 |
| 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/Y | rs374537008  |
-0.561 | 0.995 | N | 0.742 | 0.42 | None | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 6.46E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| S/Y | rs374537008 |
-0.561 | 0.995 | N | 0.742 | 0.42 | None | gnomAD-4.0.0 | 1.20033E-06 | None | None | None | None | N | None | 6.33473E-05 | 0 | None | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.0844 | likely_benign | 0.0849 | benign | -0.472 | Destabilizing | 0.78 | D | 0.535 | neutral | N | 0.488154183 | None | None | N |
| S/C | 0.0948 | likely_benign | 0.0959 | benign | -1.034 | Destabilizing | 0.999 | D | 0.698 | prob.neutral | N | 0.500057147 | None | None | N |
| S/D | 0.5509 | ambiguous | 0.5678 | pathogenic | -2.04 | Highly Destabilizing | 0.851 | D | 0.573 | neutral | None | None | None | None | N |
| S/E | 0.6014 | likely_pathogenic | 0.616 | pathogenic | -1.981 | Destabilizing | 0.851 | D | 0.55 | neutral | None | None | None | None | N |
| S/F | 0.2262 | likely_benign | 0.2273 | benign | -0.906 | Destabilizing | 0.995 | D | 0.746 | deleterious | N | 0.500791163 | None | None | N |
| S/G | 0.122 | likely_benign | 0.1163 | benign | -0.683 | Destabilizing | 0.851 | D | 0.545 | neutral | None | None | None | None | N |
| S/H | 0.2679 | likely_benign | 0.2789 | benign | -1.181 | Destabilizing | 0.988 | D | 0.721 | prob.delet. | None | None | None | None | N |
| S/I | 0.2451 | likely_benign | 0.2478 | benign | -0.012 | Destabilizing | 0.988 | D | 0.763 | deleterious | None | None | None | None | N |
| S/K | 0.5308 | ambiguous | 0.564 | pathogenic | -0.587 | Destabilizing | 0.132 | N | 0.353 | neutral | None | None | None | None | N |
| S/L | 0.12 | likely_benign | 0.1228 | benign | -0.012 | Destabilizing | 0.959 | D | 0.687 | prob.neutral | None | None | None | None | N |
| S/M | 0.1838 | likely_benign | 0.1913 | benign | 0.029 | Stabilizing | 0.999 | D | 0.707 | prob.neutral | None | None | None | None | N |
| S/N | 0.1542 | likely_benign | 0.1595 | benign | -1.099 | Destabilizing | 0.034 | N | 0.351 | neutral | None | None | None | None | N |
| S/P | 0.9808 | likely_pathogenic | 0.9839 | pathogenic | -0.135 | Destabilizing | 0.995 | D | 0.731 | prob.delet. | D | 0.547368473 | None | None | N |
| S/Q | 0.4691 | ambiguous | 0.4932 | ambiguous | -1.295 | Destabilizing | 0.507 | D | 0.365 | neutral | None | None | None | None | N |
| S/R | 0.4539 | ambiguous | 0.48 | ambiguous | -0.47 | Destabilizing | 0.851 | D | 0.68 | prob.neutral | None | None | None | None | N |
| S/T | 0.0732 | likely_benign | 0.0777 | benign | -0.779 | Destabilizing | 0.896 | D | 0.555 | neutral | D | 0.526066496 | None | None | N |
| S/V | 0.2311 | likely_benign | 0.2382 | benign | -0.135 | Destabilizing | 0.988 | D | 0.73 | prob.delet. | None | None | None | None | N |
| S/W | 0.4148 | ambiguous | 0.4087 | ambiguous | -1.099 | Destabilizing | 0.999 | D | 0.783 | deleterious | None | None | None | None | N |
| S/Y | 0.2038 | likely_benign | 0.1975 | benign | -0.639 | Destabilizing | 0.995 | D | 0.742 | deleterious | N | 0.495498017 | 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.