Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21228 | 63907;63908;63909 | chr2:178587627;178587626;178587625 | chr2:179452354;179452353;179452352 |
| N2AB | 19587 | 58984;58985;58986 | chr2:178587627;178587626;178587625 | chr2:179452354;179452353;179452352 |
| N2A | 18660 | 56203;56204;56205 | chr2:178587627;178587626;178587625 | chr2:179452354;179452353;179452352 |
| N2B | 12163 | 36712;36713;36714 | chr2:178587627;178587626;178587625 | chr2:179452354;179452353;179452352 |
| Novex-1 | 12288 | 37087;37088;37089 | chr2:178587627;178587626;178587625 | chr2:179452354;179452353;179452352 |
| Novex-2 | 12355 | 37288;37289;37290 | chr2:178587627;178587626;178587625 | chr2:179452354;179452353;179452352 |
| 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/K | None | None | 0.994 | N | 0.563 | 0.526 | 0.808737173022 | gnomAD-4.0.0 | 6.84639E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.65793E-05 |
| M/T | rs1397983700  |
None | 0.994 | N | 0.563 | 0.512 | 0.812414231654 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.92E-06 | 0 |
| M/T | rs1397983700 |
None | 0.994 | N | 0.563 | 0.512 | 0.812414231654 | gnomAD-4.0.0 | 6.84639E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99724E-07 | 0 | 0 |
| M/V | None | None | 0.985 | N | 0.45 | 0.446 | 0.703477315268 | gnomAD-4.0.0 | 1.36927E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79946E-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 | 0.7019 | likely_pathogenic | 0.6309 | pathogenic | -2.066 | Highly Destabilizing | 0.989 | D | 0.529 | neutral | None | None | None | None | N |
| M/C | 0.8527 | likely_pathogenic | 0.8223 | pathogenic | -1.497 | Destabilizing | 1.0 | D | 0.621 | neutral | None | None | None | None | N |
| M/D | 0.971 | likely_pathogenic | 0.9652 | pathogenic | -0.922 | Destabilizing | 0.999 | D | 0.699 | prob.neutral | None | None | None | None | N |
| M/E | 0.8365 | likely_pathogenic | 0.802 | pathogenic | -0.795 | Destabilizing | 0.999 | D | 0.604 | neutral | None | None | None | None | N |
| M/F | 0.6339 | likely_pathogenic | 0.5785 | pathogenic | -0.719 | Destabilizing | 0.999 | D | 0.473 | neutral | None | None | None | None | N |
| M/G | 0.9217 | likely_pathogenic | 0.902 | pathogenic | -2.473 | Highly Destabilizing | 0.995 | D | 0.63 | neutral | None | None | None | None | N |
| M/H | 0.7524 | likely_pathogenic | 0.7107 | pathogenic | -1.665 | Destabilizing | 1.0 | D | 0.669 | neutral | None | None | None | None | N |
| M/I | 0.8036 | likely_pathogenic | 0.7603 | pathogenic | -0.951 | Destabilizing | 0.985 | D | 0.481 | neutral | N | 0.461713947 | None | None | N |
| M/K | 0.5816 | likely_pathogenic | 0.55 | ambiguous | -0.953 | Destabilizing | 0.994 | D | 0.563 | neutral | N | 0.451574311 | None | None | N |
| M/L | 0.2969 | likely_benign | 0.2662 | benign | -0.951 | Destabilizing | 0.927 | D | 0.28 | neutral | N | 0.463831532 | None | None | N |
| M/N | 0.8758 | likely_pathogenic | 0.8554 | pathogenic | -1.008 | Destabilizing | 0.999 | D | 0.673 | neutral | None | None | None | None | N |
| M/P | 0.9898 | likely_pathogenic | 0.9892 | pathogenic | -1.299 | Destabilizing | 0.999 | D | 0.674 | neutral | None | None | None | None | N |
| M/Q | 0.5483 | ambiguous | 0.5137 | ambiguous | -0.906 | Destabilizing | 0.999 | D | 0.475 | neutral | None | None | None | None | N |
| M/R | 0.598 | likely_pathogenic | 0.5535 | ambiguous | -0.68 | Destabilizing | 0.998 | D | 0.576 | neutral | N | 0.459289717 | None | None | N |
| M/S | 0.7384 | likely_pathogenic | 0.6809 | pathogenic | -1.683 | Destabilizing | 0.995 | D | 0.529 | neutral | None | None | None | None | N |
| M/T | 0.5441 | ambiguous | 0.4543 | ambiguous | -1.435 | Destabilizing | 0.994 | D | 0.563 | neutral | N | 0.458038924 | None | None | N |
| M/V | 0.2001 | likely_benign | 0.1678 | benign | -1.299 | Destabilizing | 0.985 | D | 0.45 | neutral | N | 0.461407303 | None | None | N |
| M/W | 0.8976 | likely_pathogenic | 0.8805 | pathogenic | -0.805 | Destabilizing | 1.0 | D | 0.632 | neutral | None | None | None | None | N |
| M/Y | 0.7903 | likely_pathogenic | 0.7606 | pathogenic | -0.836 | Destabilizing | 0.999 | D | 0.633 | 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.