Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 33228 | 99907;99908;99909 | chr2:178537525;178537524;178537523 | chr2:179402252;179402251;179402250 |
| N2AB | 31587 | 94984;94985;94986 | chr2:178537525;178537524;178537523 | chr2:179402252;179402251;179402250 |
| N2A | 30660 | 92203;92204;92205 | chr2:178537525;178537524;178537523 | chr2:179402252;179402251;179402250 |
| N2B | 24163 | 72712;72713;72714 | chr2:178537525;178537524;178537523 | chr2:179402252;179402251;179402250 |
| Novex-1 | 24288 | 73087;73088;73089 | chr2:178537525;178537524;178537523 | chr2:179402252;179402251;179402250 |
| Novex-2 | 24355 | 73288;73289;73290 | chr2:178537525;178537524;178537523 | chr2:179402252;179402251;179402250 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/I | None | None | None | N | 0.188 | 0.122 | 0.245101548738 | gnomAD-4.0.0 | 2.40064E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.625E-06 | 0 | 0 |
| M/T | None | None | 0.091 | N | 0.443 | 0.36 | 0.788166398384 | gnomAD-4.0.0 | 1.5914E-06 | None | None | None | None | I | None | 5.65675E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| M/V | None | None | 0.002 | N | 0.286 | 0.187 | 0.380394304726 | gnomAD-4.0.0 | 1.59144E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.8584E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.5121 | ambiguous | 0.5456 | ambiguous | -2.345 | Highly Destabilizing | 0.162 | N | 0.363 | neutral | None | None | None | None | I |
| M/C | 0.7959 | likely_pathogenic | 0.7979 | pathogenic | -1.865 | Destabilizing | 0.959 | D | 0.585 | neutral | None | None | None | None | I |
| M/D | 0.9747 | likely_pathogenic | 0.9763 | pathogenic | -1.28 | Destabilizing | 0.395 | N | 0.645 | neutral | None | None | None | None | I |
| M/E | 0.8483 | likely_pathogenic | 0.8661 | pathogenic | -1.162 | Destabilizing | 0.209 | N | 0.58 | neutral | None | None | None | None | I |
| M/F | 0.4606 | ambiguous | 0.5196 | ambiguous | -1.051 | Destabilizing | 0.02 | N | 0.413 | neutral | None | None | None | None | I |
| M/G | 0.8632 | likely_pathogenic | 0.8773 | pathogenic | -2.758 | Highly Destabilizing | 0.685 | D | 0.581 | neutral | None | None | None | None | I |
| M/H | 0.8694 | likely_pathogenic | 0.8869 | pathogenic | -1.992 | Destabilizing | 0.906 | D | 0.68 | prob.neutral | None | None | None | None | I |
| M/I | 0.1331 | likely_benign | 0.2052 | benign | -1.206 | Destabilizing | None | N | 0.188 | neutral | N | 0.323007207 | None | None | I |
| M/K | 0.5987 | likely_pathogenic | 0.6506 | pathogenic | -1.134 | Destabilizing | 0.233 | N | 0.456 | neutral | N | 0.430663108 | None | None | I |
| M/L | 0.1754 | likely_benign | 0.2187 | benign | -1.206 | Destabilizing | 0.001 | N | 0.219 | neutral | N | 0.417539095 | None | None | I |
| M/N | 0.8065 | likely_pathogenic | 0.8291 | pathogenic | -1.165 | Destabilizing | 0.666 | D | 0.617 | neutral | None | None | None | None | I |
| M/P | 0.8753 | likely_pathogenic | 0.8718 | pathogenic | -1.562 | Destabilizing | 0.666 | D | 0.617 | neutral | None | None | None | None | I |
| M/Q | 0.597 | likely_pathogenic | 0.6029 | pathogenic | -1.087 | Destabilizing | 0.733 | D | 0.462 | neutral | None | None | None | None | I |
| M/R | 0.609 | likely_pathogenic | 0.6829 | pathogenic | -0.874 | Destabilizing | 0.395 | N | 0.523 | neutral | N | 0.468103989 | None | None | I |
| M/S | 0.7006 | likely_pathogenic | 0.7183 | pathogenic | -1.835 | Destabilizing | 0.473 | N | 0.454 | neutral | None | None | None | None | I |
| M/T | 0.4188 | ambiguous | 0.5146 | ambiguous | -1.591 | Destabilizing | 0.091 | N | 0.443 | neutral | N | 0.448902152 | None | None | I |
| M/V | 0.0664 | likely_benign | 0.0797 | benign | -1.562 | Destabilizing | 0.002 | N | 0.286 | neutral | N | 0.351281526 | None | None | I |
| M/W | 0.9104 | likely_pathogenic | 0.9334 | pathogenic | -1.104 | Destabilizing | 0.992 | D | 0.581 | neutral | None | None | None | None | I |
| M/Y | 0.8577 | likely_pathogenic | 0.8802 | pathogenic | -1.156 | Destabilizing | 0.548 | D | 0.517 | neutral | 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.