Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22724 | 68395;68396;68397 | chr2:178578860;178578859;178578858 | chr2:179443587;179443586;179443585 |
| N2AB | 21083 | 63472;63473;63474 | chr2:178578860;178578859;178578858 | chr2:179443587;179443586;179443585 |
| N2A | 20156 | 60691;60692;60693 | chr2:178578860;178578859;178578858 | chr2:179443587;179443586;179443585 |
| N2B | 13659 | 41200;41201;41202 | chr2:178578860;178578859;178578858 | chr2:179443587;179443586;179443585 |
| Novex-1 | 13784 | 41575;41576;41577 | chr2:178578860;178578859;178578858 | chr2:179443587;179443586;179443585 |
| Novex-2 | 13851 | 41776;41777;41778 | chr2:178578860;178578859;178578858 | chr2:179443587;179443586;179443585 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/C | rs1387896930  |
None | 1.0 | N | 0.787 | 0.52 | 0.414150184683 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.66327E-05 |
| Y/H | rs756070724 |
0.343 | 1.0 | N | 0.696 | 0.513 | 0.311387274539 | gnomAD-2.1.1 | 1.61E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 1.67523E-04 | None | 0 | None | 0 | 8.9E-06 | 0 |
| Y/H | rs756070724 |
0.343 | 1.0 | N | 0.696 | 0.513 | 0.311387274539 | gnomAD-4.0.0 | 4.10686E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 7.56773E-05 | None | 0 | 0 | 2.69924E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/A | 0.9594 | likely_pathogenic | 0.9623 | pathogenic | -0.822 | Destabilizing | 1.0 | D | 0.694 | prob.neutral | None | None | None | None | I |
| Y/C | 0.6674 | likely_pathogenic | 0.7271 | pathogenic | 0.05 | Stabilizing | 1.0 | D | 0.787 | deleterious | N | 0.497066167 | None | None | I |
| Y/D | 0.9148 | likely_pathogenic | 0.9365 | pathogenic | 0.926 | Stabilizing | 1.0 | D | 0.762 | deleterious | N | 0.474416523 | None | None | I |
| Y/E | 0.9822 | likely_pathogenic | 0.9853 | pathogenic | 0.915 | Stabilizing | 1.0 | D | 0.74 | deleterious | None | None | None | None | I |
| Y/F | 0.1651 | likely_benign | 0.1587 | benign | -0.406 | Destabilizing | 0.999 | D | 0.486 | neutral | N | 0.485310378 | None | None | I |
| Y/G | 0.9378 | likely_pathogenic | 0.9478 | pathogenic | -1.024 | Destabilizing | 1.0 | D | 0.727 | prob.delet. | None | None | None | None | I |
| Y/H | 0.7253 | likely_pathogenic | 0.7762 | pathogenic | 0.127 | Stabilizing | 1.0 | D | 0.696 | prob.neutral | N | 0.511283471 | None | None | I |
| Y/I | 0.9289 | likely_pathogenic | 0.9248 | pathogenic | -0.302 | Destabilizing | 1.0 | D | 0.722 | prob.delet. | None | None | None | None | I |
| Y/K | 0.9828 | likely_pathogenic | 0.9854 | pathogenic | 0.148 | Stabilizing | 1.0 | D | 0.739 | prob.delet. | None | None | None | None | I |
| Y/L | 0.8977 | likely_pathogenic | 0.8761 | pathogenic | -0.302 | Destabilizing | 0.999 | D | 0.698 | prob.neutral | None | None | None | None | I |
| Y/M | 0.9371 | likely_pathogenic | 0.933 | pathogenic | -0.113 | Destabilizing | 1.0 | D | 0.719 | prob.delet. | None | None | None | None | I |
| Y/N | 0.7513 | likely_pathogenic | 0.809 | pathogenic | -0.011 | Destabilizing | 1.0 | D | 0.768 | deleterious | N | 0.466934558 | None | None | I |
| Y/P | 0.9968 | likely_pathogenic | 0.9962 | pathogenic | -0.456 | Destabilizing | 1.0 | D | 0.768 | deleterious | None | None | None | None | I |
| Y/Q | 0.971 | likely_pathogenic | 0.9758 | pathogenic | 0.023 | Stabilizing | 1.0 | D | 0.737 | prob.delet. | None | None | None | None | I |
| Y/R | 0.9601 | likely_pathogenic | 0.9642 | pathogenic | 0.441 | Stabilizing | 1.0 | D | 0.773 | deleterious | None | None | None | None | I |
| Y/S | 0.8978 | likely_pathogenic | 0.9116 | pathogenic | -0.5 | Destabilizing | 1.0 | D | 0.745 | deleterious | N | 0.507877806 | None | None | I |
| Y/T | 0.962 | likely_pathogenic | 0.9678 | pathogenic | -0.418 | Destabilizing | 1.0 | D | 0.742 | deleterious | None | None | None | None | I |
| Y/V | 0.8761 | likely_pathogenic | 0.857 | pathogenic | -0.456 | Destabilizing | 1.0 | D | 0.701 | prob.neutral | None | None | None | None | I |
| Y/W | 0.6636 | likely_pathogenic | 0.6829 | pathogenic | -0.467 | Destabilizing | 1.0 | D | 0.684 | prob.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.