Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22067 | 66424;66425;66426 | chr2:178582170;178582169;178582168 | chr2:179446897;179446896;179446895 |
| N2AB | 20426 | 61501;61502;61503 | chr2:178582170;178582169;178582168 | chr2:179446897;179446896;179446895 |
| N2A | 19499 | 58720;58721;58722 | chr2:178582170;178582169;178582168 | chr2:179446897;179446896;179446895 |
| N2B | 13002 | 39229;39230;39231 | chr2:178582170;178582169;178582168 | chr2:179446897;179446896;179446895 |
| Novex-1 | 13127 | 39604;39605;39606 | chr2:178582170;178582169;178582168 | chr2:179446897;179446896;179446895 |
| Novex-2 | 13194 | 39805;39806;39807 | chr2:178582170;178582169;178582168 | chr2:179446897;179446896;179446895 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/T | rs368042545  |
-1.145 | 0.124 | N | 0.433 | 0.254 | None | gnomAD-2.1.1 | 8.11E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.8E-05 | 0 |
| I/T | rs368042545 |
-1.145 | 0.124 | N | 0.433 | 0.254 | None | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| I/T | rs368042545 |
-1.145 | 0.124 | N | 0.433 | 0.254 | None | gnomAD-4.0.0 | 1.55024E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.95002E-05 | 0 | 3.2039E-05 |
| I/V | rs2154177929 |
None | None | N | 0.095 | 0.107 | 0.241078983079 | gnomAD-4.0.0 | 1.59345E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.8953E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.5705 | likely_pathogenic | 0.544 | ambiguous | -1.738 | Destabilizing | 0.072 | N | 0.455 | neutral | None | None | None | None | N |
| I/C | 0.7446 | likely_pathogenic | 0.7319 | pathogenic | -1.223 | Destabilizing | 0.909 | D | 0.476 | neutral | None | None | None | None | N |
| I/D | 0.9359 | likely_pathogenic | 0.9226 | pathogenic | -2.045 | Highly Destabilizing | 0.726 | D | 0.609 | neutral | None | None | None | None | N |
| I/E | 0.8189 | likely_pathogenic | 0.7967 | pathogenic | -2.066 | Highly Destabilizing | 0.726 | D | 0.583 | neutral | None | None | None | None | N |
| I/F | 0.4461 | ambiguous | 0.4141 | ambiguous | -1.552 | Destabilizing | 0.567 | D | 0.447 | neutral | None | None | None | None | N |
| I/G | 0.8841 | likely_pathogenic | 0.8663 | pathogenic | -2.031 | Highly Destabilizing | 0.726 | D | 0.533 | neutral | None | None | None | None | N |
| I/H | 0.8125 | likely_pathogenic | 0.8048 | pathogenic | -1.363 | Destabilizing | 0.968 | D | 0.624 | neutral | None | None | None | None | N |
| I/K | 0.6284 | likely_pathogenic | 0.6035 | pathogenic | -1.169 | Destabilizing | 0.667 | D | 0.587 | neutral | N | 0.521580609 | None | None | N |
| I/L | 0.2838 | likely_benign | 0.2629 | benign | -1.003 | Destabilizing | 0.025 | N | 0.218 | neutral | N | 0.516942793 | None | None | N |
| I/M | 0.2076 | likely_benign | 0.1922 | benign | -0.707 | Destabilizing | 0.497 | N | 0.489 | neutral | N | 0.481919077 | None | None | N |
| I/N | 0.5991 | likely_pathogenic | 0.5417 | ambiguous | -1.074 | Destabilizing | 0.89 | D | 0.613 | neutral | None | None | None | None | N |
| I/P | 0.8432 | likely_pathogenic | 0.8169 | pathogenic | -1.22 | Destabilizing | 0.89 | D | 0.611 | neutral | None | None | None | None | N |
| I/Q | 0.6832 | likely_pathogenic | 0.6758 | pathogenic | -1.356 | Destabilizing | 0.89 | D | 0.622 | neutral | None | None | None | None | N |
| I/R | 0.5494 | ambiguous | 0.533 | ambiguous | -0.54 | Destabilizing | 0.667 | D | 0.617 | neutral | N | 0.511979691 | None | None | N |
| I/S | 0.5648 | likely_pathogenic | 0.5106 | ambiguous | -1.567 | Destabilizing | 0.567 | D | 0.489 | neutral | None | None | None | None | N |
| I/T | 0.3296 | likely_benign | 0.3277 | benign | -1.482 | Destabilizing | 0.124 | N | 0.433 | neutral | N | 0.519175022 | None | None | N |
| I/V | 0.0733 | likely_benign | 0.0746 | benign | -1.22 | Destabilizing | None | N | 0.095 | neutral | N | 0.423029768 | None | None | N |
| I/W | 0.9525 | likely_pathogenic | 0.9484 | pathogenic | -1.663 | Destabilizing | 0.968 | D | 0.721 | prob.delet. | None | None | None | None | N |
| I/Y | 0.802 | likely_pathogenic | 0.7645 | pathogenic | -1.386 | Destabilizing | 0.726 | D | 0.501 | 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.