Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20856 | 62791;62792;62793 | chr2:178589159;178589158;178589157 | chr2:179453886;179453885;179453884 |
| N2AB | 19215 | 57868;57869;57870 | chr2:178589159;178589158;178589157 | chr2:179453886;179453885;179453884 |
| N2A | 18288 | 55087;55088;55089 | chr2:178589159;178589158;178589157 | chr2:179453886;179453885;179453884 |
| N2B | 11791 | 35596;35597;35598 | chr2:178589159;178589158;178589157 | chr2:179453886;179453885;179453884 |
| Novex-1 | 11916 | 35971;35972;35973 | chr2:178589159;178589158;178589157 | chr2:179453886;179453885;179453884 |
| Novex-2 | 11983 | 36172;36173;36174 | chr2:178589159;178589158;178589157 | chr2:179453886;179453885;179453884 |
| 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 | rs373867080  |
-0.008 | 0.991 | N | 0.777 | 0.326 | None | gnomAD-2.1.1 | 5.72E-05 | None | None | None | None | N | None | 4.96032E-04 | 1.1325E-04 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| Y/C | rs373867080 |
-0.008 | 0.991 | N | 0.777 | 0.326 | None | gnomAD-3.1.2 | 1.70933E-04 | None | None | None | None | N | None | 6.2711E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| Y/C | rs373867080 |
-0.008 | 0.991 | N | 0.777 | 0.326 | None | gnomAD-4.0.0 | 3.03734E-05 | None | None | None | None | N | None | 6.14005E-04 | 5.00317E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| Y/H | rs2049698441 |
None | 0.908 | N | 0.725 | 0.323 | 0.438278051908 | gnomAD-4.0.0 | 2.40064E-06 | None | None | None | None | N | None | 1.26695E-04 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 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 | 0.5204 | ambiguous | 0.5288 | ambiguous | -0.871 | Destabilizing | 0.648 | D | 0.685 | prob.neutral | None | None | None | None | N |
| Y/C | 0.1923 | likely_benign | 0.2146 | benign | -0.283 | Destabilizing | 0.991 | D | 0.777 | deleterious | N | 0.495135874 | None | None | N |
| Y/D | 0.5821 | likely_pathogenic | 0.5855 | pathogenic | 0.538 | Stabilizing | 0.968 | D | 0.747 | deleterious | N | 0.422464912 | None | None | N |
| Y/E | 0.7467 | likely_pathogenic | 0.761 | pathogenic | 0.542 | Stabilizing | 0.929 | D | 0.76 | deleterious | None | None | None | None | N |
| Y/F | 0.0972 | likely_benign | 0.0907 | benign | -0.341 | Destabilizing | 0.004 | N | 0.348 | neutral | N | 0.410826554 | None | None | N |
| Y/G | 0.5981 | likely_pathogenic | 0.5817 | pathogenic | -1.07 | Destabilizing | 0.929 | D | 0.737 | prob.delet. | None | None | None | None | N |
| Y/H | 0.2874 | likely_benign | 0.2872 | benign | 0.173 | Stabilizing | 0.908 | D | 0.725 | prob.delet. | N | 0.4384158 | None | None | N |
| Y/I | 0.5418 | ambiguous | 0.5195 | ambiguous | -0.349 | Destabilizing | 0.764 | D | 0.731 | prob.delet. | None | None | None | None | N |
| Y/K | 0.7788 | likely_pathogenic | 0.7758 | pathogenic | -0.198 | Destabilizing | 0.929 | D | 0.761 | deleterious | None | None | None | None | N |
| Y/L | 0.5506 | ambiguous | 0.5429 | ambiguous | -0.349 | Destabilizing | 0.48 | N | 0.633 | neutral | None | None | None | None | N |
| Y/M | 0.5715 | likely_pathogenic | 0.5931 | pathogenic | -0.374 | Destabilizing | 0.98 | D | 0.741 | deleterious | None | None | None | None | N |
| Y/N | 0.297 | likely_benign | 0.2881 | benign | -0.577 | Destabilizing | 0.968 | D | 0.765 | deleterious | N | 0.406823456 | None | None | N |
| Y/P | 0.9069 | likely_pathogenic | 0.885 | pathogenic | -0.507 | Destabilizing | 0.976 | D | 0.749 | deleterious | None | None | None | None | N |
| Y/Q | 0.6602 | likely_pathogenic | 0.6487 | pathogenic | -0.468 | Destabilizing | 0.976 | D | 0.763 | deleterious | None | None | None | None | N |
| Y/R | 0.6749 | likely_pathogenic | 0.645 | pathogenic | 0.061 | Stabilizing | 0.929 | D | 0.765 | deleterious | None | None | None | None | N |
| Y/S | 0.2442 | likely_benign | 0.2479 | benign | -0.96 | Destabilizing | 0.908 | D | 0.759 | deleterious | N | 0.382290371 | None | None | N |
| Y/T | 0.3509 | ambiguous | 0.3724 | ambiguous | -0.864 | Destabilizing | 0.929 | D | 0.767 | deleterious | None | None | None | None | N |
| Y/V | 0.3588 | ambiguous | 0.3624 | ambiguous | -0.507 | Destabilizing | 0.48 | N | 0.698 | prob.neutral | None | None | None | None | N |
| Y/W | 0.3692 | ambiguous | 0.3473 | ambiguous | -0.388 | Destabilizing | 0.98 | D | 0.707 | prob.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.