Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 34952 | 105079;105080;105081 | chr2:178531761;178531760;178531759 | chr2:179396488;179396487;179396486 |
| N2AB | 33311 | 100156;100157;100158 | chr2:178531761;178531760;178531759 | chr2:179396488;179396487;179396486 |
| N2A | 32384 | 97375;97376;97377 | chr2:178531761;178531760;178531759 | chr2:179396488;179396487;179396486 |
| N2B | 25887 | 77884;77885;77886 | chr2:178531761;178531760;178531759 | chr2:179396488;179396487;179396486 |
| Novex-1 | 26012 | 78259;78260;78261 | chr2:178531761;178531760;178531759 | chr2:179396488;179396487;179396486 |
| Novex-2 | 26079 | 78460;78461;78462 | chr2:178531761;178531760;178531759 | chr2:179396488;179396487;179396486 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/S | rs765379292  |
0.005 | 1.0 | N | 0.733 | 0.318 | 0.383590876969 | gnomAD-2.1.1 | 4.01E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.56E-05 | None | 0 | None | 0 | 0 | 0 |
| R/S | rs765379292 |
0.005 | 1.0 | N | 0.733 | 0.318 | 0.383590876969 | gnomAD-4.0.0 | 3.18178E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85755E-06 | 0 | 3.02334E-05 |
| R/T | None | None | 1.0 | N | 0.729 | 0.492 | 0.621830897814 | gnomAD-4.0.0 | 2.40064E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 3.66327E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.8586 | likely_pathogenic | 0.8664 | pathogenic | -0.24 | Destabilizing | 0.999 | D | 0.645 | neutral | None | None | None | None | N |
| R/C | 0.4903 | ambiguous | 0.5504 | ambiguous | -0.275 | Destabilizing | 1.0 | D | 0.787 | deleterious | None | None | None | None | N |
| R/D | 0.9667 | likely_pathogenic | 0.9681 | pathogenic | -0.053 | Destabilizing | 1.0 | D | 0.744 | deleterious | None | None | None | None | N |
| R/E | 0.8118 | likely_pathogenic | 0.8224 | pathogenic | 0.009 | Stabilizing | 0.999 | D | 0.684 | prob.neutral | None | None | None | None | N |
| R/F | 0.9253 | likely_pathogenic | 0.9319 | pathogenic | -0.451 | Destabilizing | 1.0 | D | 0.75 | deleterious | None | None | None | None | N |
| R/G | 0.8419 | likely_pathogenic | 0.8487 | pathogenic | -0.448 | Destabilizing | 1.0 | D | 0.685 | prob.neutral | N | 0.502658176 | None | None | N |
| R/H | 0.2653 | likely_benign | 0.2965 | benign | -0.858 | Destabilizing | 1.0 | D | 0.792 | deleterious | None | None | None | None | N |
| R/I | 0.7017 | likely_pathogenic | 0.7114 | pathogenic | 0.278 | Stabilizing | 1.0 | D | 0.76 | deleterious | None | None | None | None | N |
| R/K | 0.2804 | likely_benign | 0.3023 | benign | -0.245 | Destabilizing | 0.997 | D | 0.563 | neutral | N | 0.473547094 | None | None | N |
| R/L | 0.6748 | likely_pathogenic | 0.6802 | pathogenic | 0.278 | Stabilizing | 1.0 | D | 0.685 | prob.neutral | None | None | None | None | N |
| R/M | 0.7737 | likely_pathogenic | 0.7819 | pathogenic | -0.004 | Destabilizing | 1.0 | D | 0.732 | prob.delet. | N | 0.485314389 | None | None | N |
| R/N | 0.9221 | likely_pathogenic | 0.9274 | pathogenic | 0.134 | Stabilizing | 1.0 | D | 0.775 | deleterious | None | None | None | None | N |
| R/P | 0.9779 | likely_pathogenic | 0.9721 | pathogenic | 0.126 | Stabilizing | 1.0 | D | 0.729 | prob.delet. | None | None | None | None | N |
| R/Q | 0.2476 | likely_benign | 0.2768 | benign | -0.06 | Destabilizing | 1.0 | D | 0.763 | deleterious | None | None | None | None | N |
| R/S | 0.8781 | likely_pathogenic | 0.8917 | pathogenic | -0.371 | Destabilizing | 1.0 | D | 0.733 | prob.delet. | N | 0.473605809 | None | None | N |
| R/T | 0.7034 | likely_pathogenic | 0.7276 | pathogenic | -0.169 | Destabilizing | 1.0 | D | 0.729 | prob.delet. | N | 0.44597649 | None | None | N |
| R/V | 0.7286 | likely_pathogenic | 0.7425 | pathogenic | 0.126 | Stabilizing | 1.0 | D | 0.739 | prob.delet. | None | None | None | None | N |
| R/W | 0.6157 | likely_pathogenic | 0.628 | pathogenic | -0.39 | Destabilizing | 1.0 | D | 0.802 | deleterious | N | 0.503672134 | None | None | N |
| R/Y | 0.845 | likely_pathogenic | 0.8558 | pathogenic | 0.001 | Stabilizing | 1.0 | D | 0.759 | 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.