Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20618 | 62077;62078;62079 | chr2:178589873;178589872;178589871 | chr2:179454600;179454599;179454598 |
| N2AB | 18977 | 57154;57155;57156 | chr2:178589873;178589872;178589871 | chr2:179454600;179454599;179454598 |
| N2A | 18050 | 54373;54374;54375 | chr2:178589873;178589872;178589871 | chr2:179454600;179454599;179454598 |
| N2B | 11553 | 34882;34883;34884 | chr2:178589873;178589872;178589871 | chr2:179454600;179454599;179454598 |
| Novex-1 | 11678 | 35257;35258;35259 | chr2:178589873;178589872;178589871 | chr2:179454600;179454599;179454598 |
| Novex-2 | 11745 | 35458;35459;35460 | chr2:178589873;178589872;178589871 | chr2:179454600;179454599;179454598 |
| 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 | rs901919886  |
None | 0.801 | N | 0.466 | 0.335 | 0.649663983678 | gnomAD-4.0.0 | 2.73742E-06 | None | None | None | None | I | None | 2.98936E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79916E-06 | 0 | 1.65695E-05 |
| I/V | rs1216529341 |
-0.416 | 0.005 | N | 0.146 | 0.118 | 0.410469974859 | gnomAD-2.1.1 | 8.04E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.86E-06 | 1.65563E-04 |
| I/V | rs1216529341 |
-0.416 | 0.005 | N | 0.146 | 0.118 | 0.410469974859 | gnomAD-4.0.0 | 1.36871E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.9958E-07 | 0 | 1.65695E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.3607 | ambiguous | 0.3445 | ambiguous | -1.212 | Destabilizing | 0.525 | D | 0.457 | neutral | None | None | None | None | I |
| I/C | 0.7752 | likely_pathogenic | 0.7329 | pathogenic | -0.764 | Destabilizing | 0.998 | D | 0.539 | neutral | None | None | None | None | I |
| I/D | 0.8614 | likely_pathogenic | 0.8425 | pathogenic | -0.44 | Destabilizing | 0.991 | D | 0.603 | neutral | None | None | None | None | I |
| I/E | 0.7491 | likely_pathogenic | 0.6966 | pathogenic | -0.478 | Destabilizing | 0.974 | D | 0.575 | neutral | None | None | None | None | I |
| I/F | 0.2683 | likely_benign | 0.2539 | benign | -0.851 | Destabilizing | 0.934 | D | 0.443 | neutral | N | 0.488926686 | None | None | I |
| I/G | 0.7873 | likely_pathogenic | 0.7668 | pathogenic | -1.473 | Destabilizing | 0.974 | D | 0.567 | neutral | None | None | None | None | I |
| I/H | 0.6942 | likely_pathogenic | 0.6432 | pathogenic | -0.598 | Destabilizing | 0.998 | D | 0.587 | neutral | None | None | None | None | I |
| I/K | 0.5532 | ambiguous | 0.4813 | ambiguous | -0.745 | Destabilizing | 0.974 | D | 0.569 | neutral | None | None | None | None | I |
| I/L | 0.1395 | likely_benign | 0.1392 | benign | -0.604 | Destabilizing | 0.267 | N | 0.231 | neutral | N | 0.472399795 | None | None | I |
| I/M | 0.1185 | likely_benign | 0.1145 | benign | -0.497 | Destabilizing | 0.136 | N | 0.161 | neutral | N | 0.457875847 | None | None | I |
| I/N | 0.4225 | ambiguous | 0.4157 | ambiguous | -0.545 | Destabilizing | 0.989 | D | 0.606 | neutral | N | 0.458779924 | None | None | I |
| I/P | 0.6633 | likely_pathogenic | 0.6522 | pathogenic | -0.773 | Destabilizing | 0.991 | D | 0.606 | neutral | None | None | None | None | I |
| I/Q | 0.576 | likely_pathogenic | 0.5046 | ambiguous | -0.75 | Destabilizing | 0.974 | D | 0.607 | neutral | None | None | None | None | I |
| I/R | 0.4751 | ambiguous | 0.3915 | ambiguous | -0.133 | Destabilizing | 0.974 | D | 0.607 | neutral | None | None | None | None | I |
| I/S | 0.4205 | ambiguous | 0.383 | ambiguous | -1.135 | Destabilizing | 0.891 | D | 0.557 | neutral | N | 0.471554433 | None | None | I |
| I/T | 0.2197 | likely_benign | 0.2128 | benign | -1.061 | Destabilizing | 0.801 | D | 0.466 | neutral | N | 0.391728213 | None | None | I |
| I/V | 0.0724 | likely_benign | 0.0757 | benign | -0.773 | Destabilizing | 0.005 | N | 0.146 | neutral | N | 0.404964082 | None | None | I |
| I/W | 0.8781 | likely_pathogenic | 0.8514 | pathogenic | -0.863 | Destabilizing | 0.998 | D | 0.617 | neutral | None | None | None | None | I |
| I/Y | 0.6714 | likely_pathogenic | 0.63 | pathogenic | -0.647 | Destabilizing | 0.991 | D | 0.555 | 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.