Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20663 | 62212;62213;62214 | chr2:178589738;178589737;178589736 | chr2:179454465;179454464;179454463 |
| N2AB | 19022 | 57289;57290;57291 | chr2:178589738;178589737;178589736 | chr2:179454465;179454464;179454463 |
| N2A | 18095 | 54508;54509;54510 | chr2:178589738;178589737;178589736 | chr2:179454465;179454464;179454463 |
| N2B | 11598 | 35017;35018;35019 | chr2:178589738;178589737;178589736 | chr2:179454465;179454464;179454463 |
| Novex-1 | 11723 | 35392;35393;35394 | chr2:178589738;178589737;178589736 | chr2:179454465;179454464;179454463 |
| Novex-2 | 11790 | 35593;35594;35595 | chr2:178589738;178589737;178589736 | chr2:179454465;179454464;179454463 |
| 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 | rs1297355642  |
-0.58 | 0.976 | N | 0.51 | 0.291 | 0.524584940466 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/T | rs1297355642 |
-0.58 | 0.976 | N | 0.51 | 0.291 | 0.524584940466 | gnomAD-4.0.0 | 1.5917E-06 | None | None | None | None | N | None | 0 | 2.28686E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | None | None | 0.188 | N | 0.138 | 0.105 | 0.362160248664 | gnomAD-4.0.0 | 6.84298E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99575E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.6506 | likely_pathogenic | 0.5363 | ambiguous | -1.404 | Destabilizing | 0.982 | D | 0.385 | neutral | None | None | None | None | N |
| I/C | 0.8603 | likely_pathogenic | 0.7876 | pathogenic | -0.746 | Destabilizing | 1.0 | D | 0.513 | neutral | None | None | None | None | N |
| I/D | 0.9554 | likely_pathogenic | 0.9082 | pathogenic | -0.947 | Destabilizing | 0.999 | D | 0.777 | deleterious | None | None | None | None | N |
| I/E | 0.8535 | likely_pathogenic | 0.7253 | pathogenic | -1.009 | Destabilizing | 0.999 | D | 0.808 | deleterious | None | None | None | None | N |
| I/F | 0.5208 | ambiguous | 0.4042 | ambiguous | -1.229 | Destabilizing | 0.997 | D | 0.525 | neutral | N | 0.494119075 | None | None | N |
| I/G | 0.9039 | likely_pathogenic | 0.8422 | pathogenic | -1.654 | Destabilizing | 0.999 | D | 0.813 | deleterious | None | None | None | None | N |
| I/H | 0.8945 | likely_pathogenic | 0.8034 | pathogenic | -0.947 | Destabilizing | 1.0 | D | 0.773 | deleterious | None | None | None | None | N |
| I/K | 0.6844 | likely_pathogenic | 0.4578 | ambiguous | -0.877 | Destabilizing | 0.999 | D | 0.803 | deleterious | None | None | None | None | N |
| I/L | 0.2403 | likely_benign | 0.1843 | benign | -0.828 | Destabilizing | 0.787 | D | 0.343 | neutral | N | 0.436358851 | None | None | N |
| I/M | 0.2128 | likely_benign | 0.1662 | benign | -0.51 | Destabilizing | 0.997 | D | 0.478 | neutral | N | 0.446250557 | None | None | N |
| I/N | 0.7111 | likely_pathogenic | 0.5491 | ambiguous | -0.595 | Destabilizing | 0.999 | D | 0.781 | deleterious | N | 0.465009676 | None | None | N |
| I/P | 0.9742 | likely_pathogenic | 0.9547 | pathogenic | -0.987 | Destabilizing | 0.999 | D | 0.812 | deleterious | None | None | None | None | N |
| I/Q | 0.7091 | likely_pathogenic | 0.5518 | ambiguous | -0.868 | Destabilizing | 0.999 | D | 0.723 | deleterious | None | None | None | None | N |
| I/R | 0.6124 | likely_pathogenic | 0.4114 | ambiguous | -0.226 | Destabilizing | 0.999 | D | 0.777 | deleterious | None | None | None | None | N |
| I/S | 0.6649 | likely_pathogenic | 0.5337 | ambiguous | -1.113 | Destabilizing | 0.997 | D | 0.719 | prob.delet. | N | 0.450578942 | None | None | N |
| I/T | 0.5184 | ambiguous | 0.3545 | ambiguous | -1.069 | Destabilizing | 0.976 | D | 0.51 | neutral | N | 0.398611326 | None | None | N |
| I/V | 0.0932 | likely_benign | 0.0786 | benign | -0.987 | Destabilizing | 0.188 | N | 0.138 | neutral | N | 0.405537298 | None | None | N |
| I/W | 0.9587 | likely_pathogenic | 0.9361 | pathogenic | -1.25 | Destabilizing | 1.0 | D | 0.724 | deleterious | None | None | None | None | N |
| I/Y | 0.864 | likely_pathogenic | 0.791 | pathogenic | -1.027 | Destabilizing | 0.999 | D | 0.448 | 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.