Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32369 | 97330;97331;97332 | chr2:178542749;178542748;178542747 | chr2:179407476;179407475;179407474 |
| N2AB | 30728 | 92407;92408;92409 | chr2:178542749;178542748;178542747 | chr2:179407476;179407475;179407474 |
| N2A | 29801 | 89626;89627;89628 | chr2:178542749;178542748;178542747 | chr2:179407476;179407475;179407474 |
| N2B | 23304 | 70135;70136;70137 | chr2:178542749;178542748;178542747 | chr2:179407476;179407475;179407474 |
| Novex-1 | 23429 | 70510;70511;70512 | chr2:178542749;178542748;178542747 | chr2:179407476;179407475;179407474 |
| Novex-2 | 23496 | 70711;70712;70713 | chr2:178542749;178542748;178542747 | chr2:179407476;179407475;179407474 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/I | rs559194338  |
0.172 | 0.056 | N | 0.416 | 0.306 | 0.363356657567 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 6.46E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| T/I | rs559194338 |
0.172 | 0.056 | N | 0.416 | 0.306 | 0.363356657567 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| T/I | rs559194338 |
0.172 | 0.056 | N | 0.416 | 0.306 | 0.363356657567 | 1000 genomes | 3.99361E-04 | None | None | None | None | N | None | 1.5E-03 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| T/I | rs559194338 |
0.172 | 0.056 | N | 0.416 | 0.306 | 0.363356657567 | gnomAD-4.0.0 | 1.85898E-06 | None | None | None | None | N | None | 3.99893E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| T/N | None | None | 0.994 | N | 0.622 | 0.437 | 0.562316820711 | gnomAD-4.0.0 | 1.36843E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79897E-06 | 0 | 0 |
| T/S | None | None | 0.805 | N | 0.475 | 0.216 | 0.267299060538 | gnomAD-4.0.0 | 1.59122E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85829E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.1189 | likely_benign | 0.1138 | benign | -0.619 | Destabilizing | 0.099 | N | 0.329 | neutral | N | 0.442970684 | None | None | N |
| T/C | 0.5928 | likely_pathogenic | 0.5343 | ambiguous | -0.995 | Destabilizing | 0.999 | D | 0.646 | neutral | None | None | None | None | N |
| T/D | 0.965 | likely_pathogenic | 0.966 | pathogenic | -2.227 | Highly Destabilizing | 0.987 | D | 0.685 | prob.neutral | None | None | None | None | N |
| T/E | 0.9554 | likely_pathogenic | 0.9574 | pathogenic | -2.128 | Highly Destabilizing | 0.987 | D | 0.679 | prob.neutral | None | None | None | None | N |
| T/F | 0.9734 | likely_pathogenic | 0.9644 | pathogenic | -0.705 | Destabilizing | 0.975 | D | 0.691 | prob.neutral | None | None | None | None | N |
| T/G | 0.5106 | ambiguous | 0.4723 | ambiguous | -0.915 | Destabilizing | 0.916 | D | 0.639 | neutral | None | None | None | None | N |
| T/H | 0.9514 | likely_pathogenic | 0.9471 | pathogenic | -1.265 | Destabilizing | 0.999 | D | 0.678 | prob.neutral | None | None | None | None | N |
| T/I | 0.8063 | likely_pathogenic | 0.7393 | pathogenic | 0.1 | Stabilizing | 0.056 | N | 0.416 | neutral | N | 0.491244633 | None | None | N |
| T/K | 0.9598 | likely_pathogenic | 0.9613 | pathogenic | -0.786 | Destabilizing | 0.987 | D | 0.679 | prob.neutral | None | None | None | None | N |
| T/L | 0.6684 | likely_pathogenic | 0.6085 | pathogenic | 0.1 | Stabilizing | 0.437 | N | 0.516 | neutral | None | None | None | None | N |
| T/M | 0.3883 | ambiguous | 0.3329 | benign | 0.189 | Stabilizing | 0.993 | D | 0.663 | neutral | None | None | None | None | N |
| T/N | 0.6375 | likely_pathogenic | 0.6129 | pathogenic | -1.418 | Destabilizing | 0.994 | D | 0.622 | neutral | N | 0.499949151 | None | None | N |
| T/P | 0.5405 | ambiguous | 0.5289 | ambiguous | -0.108 | Destabilizing | 0.983 | D | 0.691 | prob.neutral | N | 0.508854533 | None | None | N |
| T/Q | 0.9113 | likely_pathogenic | 0.9092 | pathogenic | -1.489 | Destabilizing | 0.996 | D | 0.676 | prob.neutral | None | None | None | None | N |
| T/R | 0.9465 | likely_pathogenic | 0.9452 | pathogenic | -0.666 | Destabilizing | 0.987 | D | 0.695 | prob.neutral | None | None | None | None | N |
| T/S | 0.2334 | likely_benign | 0.2045 | benign | -1.362 | Destabilizing | 0.805 | D | 0.475 | neutral | N | 0.472605731 | None | None | N |
| T/V | 0.4884 | ambiguous | 0.4288 | ambiguous | -0.108 | Destabilizing | 0.437 | N | 0.494 | neutral | None | None | None | None | N |
| T/W | 0.9951 | likely_pathogenic | 0.9943 | pathogenic | -0.927 | Destabilizing | 0.999 | D | 0.661 | neutral | None | None | None | None | N |
| T/Y | 0.9715 | likely_pathogenic | 0.9665 | pathogenic | -0.488 | Destabilizing | 0.987 | D | 0.702 | 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.