Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 34380 | 103363;103364;103365 | chr2:178533477;178533476;178533475 | chr2:179398204;179398203;179398202 |
| N2AB | 32739 | 98440;98441;98442 | chr2:178533477;178533476;178533475 | chr2:179398204;179398203;179398202 |
| N2A | 31812 | 95659;95660;95661 | chr2:178533477;178533476;178533475 | chr2:179398204;179398203;179398202 |
| N2B | 25315 | 76168;76169;76170 | chr2:178533477;178533476;178533475 | chr2:179398204;179398203;179398202 |
| Novex-1 | 25440 | 76543;76544;76545 | chr2:178533477;178533476;178533475 | chr2:179398204;179398203;179398202 |
| Novex-2 | 25507 | 76744;76745;76746 | chr2:178533477;178533476;178533475 | chr2:179398204;179398203;179398202 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/I | rs749967687  |
-0.318 | 0.002 | N | 0.227 | 0.122 | 0.488266720666 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| V/I | rs749967687 |
-0.318 | 0.002 | N | 0.227 | 0.122 | 0.488266720666 | gnomAD-4.0.0 | 3.42213E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.69929E-06 | 2.31922E-05 | 0 |
| V/L | None | None | 0.034 | D | 0.491 | 0.124 | 0.391156786388 | gnomAD-4.0.0 | 6.84425E-07 | None | None | None | None | N | None | 0 | 2.23694E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.6519 | likely_pathogenic | 0.6719 | pathogenic | -1.676 | Destabilizing | 0.334 | N | 0.558 | neutral | N | 0.440826961 | None | None | N |
| V/C | 0.9043 | likely_pathogenic | 0.9176 | pathogenic | -1.044 | Destabilizing | 0.982 | D | 0.748 | deleterious | None | None | None | None | N |
| V/D | 0.9911 | likely_pathogenic | 0.9917 | pathogenic | -1.471 | Destabilizing | 0.781 | D | 0.815 | deleterious | D | 0.547933538 | None | None | N |
| V/E | 0.9738 | likely_pathogenic | 0.976 | pathogenic | -1.417 | Destabilizing | 0.826 | D | 0.796 | deleterious | None | None | None | None | N |
| V/F | 0.7352 | likely_pathogenic | 0.7576 | pathogenic | -1.212 | Destabilizing | 0.638 | D | 0.8 | deleterious | D | 0.538377724 | None | None | N |
| V/G | 0.9195 | likely_pathogenic | 0.927 | pathogenic | -2.063 | Highly Destabilizing | 0.781 | D | 0.801 | deleterious | N | 0.506609693 | None | None | N |
| V/H | 0.9871 | likely_pathogenic | 0.9872 | pathogenic | -1.647 | Destabilizing | 0.982 | D | 0.803 | deleterious | None | None | None | None | N |
| V/I | 0.0865 | likely_benign | 0.0851 | benign | -0.68 | Destabilizing | 0.002 | N | 0.227 | neutral | N | 0.519482532 | None | None | N |
| V/K | 0.9737 | likely_pathogenic | 0.9736 | pathogenic | -1.348 | Destabilizing | 0.826 | D | 0.8 | deleterious | None | None | None | None | N |
| V/L | 0.5065 | ambiguous | 0.5596 | ambiguous | -0.68 | Destabilizing | 0.034 | N | 0.491 | neutral | D | 0.522154691 | None | None | N |
| V/M | 0.5121 | ambiguous | 0.5461 | ambiguous | -0.49 | Destabilizing | 0.7 | D | 0.749 | deleterious | None | None | None | None | N |
| V/N | 0.9632 | likely_pathogenic | 0.9637 | pathogenic | -1.158 | Destabilizing | 0.935 | D | 0.841 | deleterious | None | None | None | None | N |
| V/P | 0.9919 | likely_pathogenic | 0.992 | pathogenic | -0.978 | Destabilizing | 0.935 | D | 0.811 | deleterious | None | None | None | None | N |
| V/Q | 0.9603 | likely_pathogenic | 0.9626 | pathogenic | -1.241 | Destabilizing | 0.935 | D | 0.821 | deleterious | None | None | None | None | N |
| V/R | 0.9496 | likely_pathogenic | 0.9531 | pathogenic | -0.928 | Destabilizing | 0.826 | D | 0.839 | deleterious | None | None | None | None | N |
| V/S | 0.8917 | likely_pathogenic | 0.8945 | pathogenic | -1.734 | Destabilizing | 0.826 | D | 0.79 | deleterious | None | None | None | None | N |
| V/T | 0.7627 | likely_pathogenic | 0.7393 | pathogenic | -1.554 | Destabilizing | 0.399 | N | 0.693 | prob.neutral | None | None | None | None | N |
| V/W | 0.9949 | likely_pathogenic | 0.9957 | pathogenic | -1.468 | Destabilizing | 0.982 | D | 0.769 | deleterious | None | None | None | None | N |
| V/Y | 0.9701 | likely_pathogenic | 0.9738 | pathogenic | -1.164 | Destabilizing | 0.826 | D | 0.798 | 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.