Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25817 | 77674;77675;77676 | chr2:178568683;178568682;178568681 | chr2:179433410;179433409;179433408 |
| N2AB | 24176 | 72751;72752;72753 | chr2:178568683;178568682;178568681 | chr2:179433410;179433409;179433408 |
| N2A | 23249 | 69970;69971;69972 | chr2:178568683;178568682;178568681 | chr2:179433410;179433409;179433408 |
| N2B | 16752 | 50479;50480;50481 | chr2:178568683;178568682;178568681 | chr2:179433410;179433409;179433408 |
| Novex-1 | 16877 | 50854;50855;50856 | chr2:178568683;178568682;178568681 | chr2:179433410;179433409;179433408 |
| Novex-2 | 16944 | 51055;51056;51057 | chr2:178568683;178568682;178568681 | chr2:179433410;179433409;179433408 |
| 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 | rs770455270  |
-2.308 | 0.549 | D | 0.701 | 0.542 | 0.624741333878 | gnomAD-2.1.1 | 1.61E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 3.58E-05 | 0 |
| I/T | rs770455270 |
-2.308 | 0.549 | D | 0.701 | 0.542 | 0.624741333878 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| I/T | rs770455270 |
-2.308 | 0.549 | D | 0.701 | 0.542 | 0.624741333878 | gnomAD-4.0.0 | 6.40999E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.19714E-05 | 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 | 0.5623 | ambiguous | 0.5139 | ambiguous | -2.219 | Highly Destabilizing | 0.25 | N | 0.693 | prob.neutral | None | None | None | None | N |
| I/C | 0.8793 | likely_pathogenic | 0.8572 | pathogenic | -1.65 | Destabilizing | 0.977 | D | 0.767 | deleterious | None | None | None | None | N |
| I/D | 0.9944 | likely_pathogenic | 0.9935 | pathogenic | -2.191 | Highly Destabilizing | 0.972 | D | 0.853 | deleterious | None | None | None | None | N |
| I/E | 0.9814 | likely_pathogenic | 0.9788 | pathogenic | -1.949 | Destabilizing | 0.92 | D | 0.823 | deleterious | None | None | None | None | N |
| I/F | 0.3548 | ambiguous | 0.3182 | benign | -1.358 | Destabilizing | 0.85 | D | 0.72 | prob.delet. | None | None | None | None | N |
| I/G | 0.9418 | likely_pathogenic | 0.9295 | pathogenic | -2.723 | Highly Destabilizing | 0.92 | D | 0.824 | deleterious | None | None | None | None | N |
| I/H | 0.9804 | likely_pathogenic | 0.9763 | pathogenic | -1.988 | Destabilizing | 0.992 | D | 0.845 | deleterious | None | None | None | None | N |
| I/K | 0.9719 | likely_pathogenic | 0.9671 | pathogenic | -1.662 | Destabilizing | 0.896 | D | 0.823 | deleterious | D | 0.529778559 | None | None | N |
| I/L | 0.1475 | likely_benign | 0.1335 | benign | -0.759 | Destabilizing | 0.002 | N | 0.273 | neutral | N | 0.459163926 | None | None | N |
| I/M | 0.1453 | likely_benign | 0.1317 | benign | -0.85 | Destabilizing | 0.81 | D | 0.664 | neutral | D | 0.534982342 | None | None | N |
| I/N | 0.9513 | likely_pathogenic | 0.9435 | pathogenic | -2.086 | Highly Destabilizing | 0.972 | D | 0.858 | deleterious | None | None | None | None | N |
| I/P | 0.9828 | likely_pathogenic | 0.9828 | pathogenic | -1.229 | Destabilizing | 0.972 | D | 0.851 | deleterious | None | None | None | None | N |
| I/Q | 0.9685 | likely_pathogenic | 0.9631 | pathogenic | -1.873 | Destabilizing | 0.972 | D | 0.86 | deleterious | None | None | None | None | N |
| I/R | 0.9524 | likely_pathogenic | 0.9436 | pathogenic | -1.568 | Destabilizing | 0.896 | D | 0.857 | deleterious | D | 0.541299449 | None | None | N |
| I/S | 0.8793 | likely_pathogenic | 0.8552 | pathogenic | -2.777 | Highly Destabilizing | 0.85 | D | 0.802 | deleterious | None | None | None | None | N |
| I/T | 0.5982 | likely_pathogenic | 0.5284 | ambiguous | -2.37 | Highly Destabilizing | 0.549 | D | 0.701 | prob.neutral | D | 0.54104596 | None | None | N |
| I/V | 0.0753 | likely_benign | 0.0697 | benign | -1.229 | Destabilizing | 0.001 | N | 0.229 | neutral | N | 0.502928638 | None | None | N |
| I/W | 0.9536 | likely_pathogenic | 0.9434 | pathogenic | -1.547 | Destabilizing | 0.992 | D | 0.843 | deleterious | None | None | None | None | N |
| I/Y | 0.8704 | likely_pathogenic | 0.8531 | pathogenic | -1.289 | Destabilizing | 0.92 | D | 0.784 | deleterious | 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.