Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14895 | 44908;44909;44910 | chr2:178624597;178624596;178624595 | chr2:179489324;179489323;179489322 |
| N2AB | 13254 | 39985;39986;39987 | chr2:178624597;178624596;178624595 | chr2:179489324;179489323;179489322 |
| N2A | 12327 | 37204;37205;37206 | chr2:178624597;178624596;178624595 | chr2:179489324;179489323;179489322 |
| N2B | 5830 | 17713;17714;17715 | chr2:178624597;178624596;178624595 | chr2:179489324;179489323;179489322 |
| Novex-1 | 5955 | 18088;18089;18090 | chr2:178624597;178624596;178624595 | chr2:179489324;179489323;179489322 |
| Novex-2 | 6022 | 18289;18290;18291 | chr2:178624597;178624596;178624595 | chr2:179489324;179489323;179489322 |
| 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/C | None | None | 0.99 | N | 0.315 | 0.262 | 0.200317383148 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 6.33473E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/I | None | None | 0.81 | N | 0.417 | 0.155 | None | gnomAD-4.0.0 | 4.78063E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 4.29947E-05 | 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 | 0.239 | likely_benign | 0.2285 | benign | -0.343 | Destabilizing | 0.25 | N | 0.377 | neutral | None | None | None | None | N |
| S/C | 0.2743 | likely_benign | 0.252 | benign | -0.359 | Destabilizing | 0.99 | D | 0.315 | neutral | N | 0.391198788 | None | None | N |
| S/D | 0.456 | ambiguous | 0.3571 | ambiguous | 0.447 | Stabilizing | 0.447 | N | 0.366 | neutral | None | None | None | None | N |
| S/E | 0.7358 | likely_pathogenic | 0.6702 | pathogenic | 0.397 | Stabilizing | 0.617 | D | 0.369 | neutral | None | None | None | None | N |
| S/F | 0.7267 | likely_pathogenic | 0.674 | pathogenic | -0.878 | Destabilizing | 0.92 | D | 0.396 | neutral | None | None | None | None | N |
| S/G | 0.0952 | likely_benign | 0.0903 | benign | -0.487 | Destabilizing | 0.201 | N | 0.369 | neutral | N | 0.348398244 | None | None | N |
| S/H | 0.5483 | ambiguous | 0.4912 | ambiguous | -0.816 | Destabilizing | 0.85 | D | 0.311 | neutral | None | None | None | None | N |
| S/I | 0.663 | likely_pathogenic | 0.5584 | ambiguous | -0.087 | Destabilizing | 0.81 | D | 0.417 | neutral | N | 0.408407779 | None | None | N |
| S/K | 0.8629 | likely_pathogenic | 0.8098 | pathogenic | -0.311 | Destabilizing | 0.447 | N | 0.372 | neutral | None | None | None | None | N |
| S/L | 0.4026 | ambiguous | 0.3307 | benign | -0.087 | Destabilizing | 0.447 | N | 0.408 | neutral | None | None | None | None | N |
| S/M | 0.4937 | ambiguous | 0.4211 | ambiguous | -0.175 | Destabilizing | 0.992 | D | 0.307 | neutral | None | None | None | None | N |
| S/N | 0.1529 | likely_benign | 0.0971 | benign | -0.214 | Destabilizing | 0.004 | N | 0.232 | neutral | N | 0.339082038 | None | None | N |
| S/P | 0.8865 | likely_pathogenic | 0.8424 | pathogenic | -0.142 | Destabilizing | 0.92 | D | 0.336 | neutral | None | None | None | None | N |
| S/Q | 0.7323 | likely_pathogenic | 0.6902 | pathogenic | -0.316 | Destabilizing | 0.85 | D | 0.373 | neutral | None | None | None | None | N |
| S/R | 0.8458 | likely_pathogenic | 0.7797 | pathogenic | -0.17 | Destabilizing | 0.81 | D | 0.33 | neutral | N | 0.453103814 | None | None | N |
| S/T | 0.1311 | likely_benign | 0.1048 | benign | -0.275 | Destabilizing | 0.002 | N | 0.151 | neutral | N | 0.352575806 | None | None | N |
| S/V | 0.6508 | likely_pathogenic | 0.5705 | pathogenic | -0.142 | Destabilizing | 0.447 | N | 0.394 | neutral | None | None | None | None | N |
| S/W | 0.729 | likely_pathogenic | 0.7017 | pathogenic | -0.947 | Destabilizing | 0.992 | D | 0.491 | neutral | None | None | None | None | N |
| S/Y | 0.5344 | ambiguous | 0.4671 | ambiguous | -0.62 | Destabilizing | 0.972 | D | 0.391 | 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.