Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1747 | 5464;5465;5466 | chr2:178776625;178776624;178776623 | chr2:179641352;179641351;179641350 |
| N2AB | 1747 | 5464;5465;5466 | chr2:178776625;178776624;178776623 | chr2:179641352;179641351;179641350 |
| N2A | 1747 | 5464;5465;5466 | chr2:178776625;178776624;178776623 | chr2:179641352;179641351;179641350 |
| N2B | 1701 | 5326;5327;5328 | chr2:178776625;178776624;178776623 | chr2:179641352;179641351;179641350 |
| Novex-1 | 1701 | 5326;5327;5328 | chr2:178776625;178776624;178776623 | chr2:179641352;179641351;179641350 |
| Novex-2 | 1701 | 5326;5327;5328 | chr2:178776625;178776624;178776623 | chr2:179641352;179641351;179641350 |
| Novex-3 | 1747 | 5464;5465;5466 | chr2:178776625;178776624;178776623 | chr2:179641352;179641351;179641350 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/T | rs935944166  |
-0.39 | 1.0 | N | 0.61 | 0.266 | 0.358540694251 | gnomAD-2.1.1 | 3.99E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.83E-06 | 0 |
| A/T | rs935944166 |
-0.39 | 1.0 | N | 0.61 | 0.266 | 0.358540694251 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 4.78011E-04 |
| A/T | rs935944166 |
-0.39 | 1.0 | N | 0.61 | 0.266 | 0.358540694251 | gnomAD-4.0.0 | 4.33709E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.08465E-06 | 0 | 1.60041E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.8924 | likely_pathogenic | 0.8571 | pathogenic | -0.806 | Destabilizing | 1.0 | D | 0.677 | prob.neutral | None | None | None | None | N |
| A/D | 0.7809 | likely_pathogenic | 0.7041 | pathogenic | -0.517 | Destabilizing | 1.0 | D | 0.723 | prob.delet. | None | None | None | None | N |
| A/E | 0.7071 | likely_pathogenic | 0.6114 | pathogenic | -0.651 | Destabilizing | 1.0 | D | 0.695 | prob.neutral | N | 0.504209644 | None | None | N |
| A/F | 0.7062 | likely_pathogenic | 0.634 | pathogenic | -0.828 | Destabilizing | 1.0 | D | 0.731 | prob.delet. | None | None | None | None | N |
| A/G | 0.3258 | likely_benign | 0.2564 | benign | -0.232 | Destabilizing | 1.0 | D | 0.509 | neutral | N | 0.502854679 | None | None | N |
| A/H | 0.7944 | likely_pathogenic | 0.7445 | pathogenic | -0.216 | Destabilizing | 1.0 | D | 0.685 | prob.neutral | None | None | None | None | N |
| A/I | 0.7502 | likely_pathogenic | 0.6398 | pathogenic | -0.305 | Destabilizing | 1.0 | D | 0.667 | neutral | None | None | None | None | N |
| A/K | 0.8917 | likely_pathogenic | 0.8439 | pathogenic | -0.595 | Destabilizing | 1.0 | D | 0.689 | prob.neutral | None | None | None | None | N |
| A/L | 0.5227 | ambiguous | 0.4295 | ambiguous | -0.305 | Destabilizing | 1.0 | D | 0.633 | neutral | None | None | None | None | N |
| A/M | 0.5634 | ambiguous | 0.4461 | ambiguous | -0.583 | Destabilizing | 1.0 | D | 0.669 | neutral | None | None | None | None | N |
| A/N | 0.5375 | ambiguous | 0.4287 | ambiguous | -0.287 | Destabilizing | 1.0 | D | 0.739 | prob.delet. | None | None | None | None | N |
| A/P | 0.5703 | likely_pathogenic | 0.4472 | ambiguous | -0.243 | Destabilizing | 1.0 | D | 0.689 | prob.neutral | N | 0.505557085 | None | None | N |
| A/Q | 0.6762 | likely_pathogenic | 0.5893 | pathogenic | -0.52 | Destabilizing | 1.0 | D | 0.703 | prob.neutral | None | None | None | None | N |
| A/R | 0.8437 | likely_pathogenic | 0.8032 | pathogenic | -0.19 | Destabilizing | 1.0 | D | 0.691 | prob.neutral | None | None | None | None | N |
| A/S | 0.1772 | likely_benign | 0.1473 | benign | -0.467 | Destabilizing | 1.0 | D | 0.514 | neutral | N | 0.490874574 | None | None | N |
| A/T | 0.3153 | likely_benign | 0.2198 | benign | -0.525 | Destabilizing | 1.0 | D | 0.61 | neutral | N | 0.508048647 | None | None | N |
| A/V | 0.4286 | ambiguous | 0.3282 | benign | -0.243 | Destabilizing | 1.0 | D | 0.568 | neutral | D | 0.55499867 | None | None | N |
| A/W | 0.9566 | likely_pathogenic | 0.9321 | pathogenic | -0.963 | Destabilizing | 1.0 | D | 0.725 | prob.delet. | None | None | None | None | N |
| A/Y | 0.7993 | likely_pathogenic | 0.7439 | pathogenic | -0.629 | Destabilizing | 1.0 | D | 0.724 | prob.delet. | 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.