Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20453 | 61582;61583;61584 | chr2:178590368;178590367;178590366 | chr2:179455095;179455094;179455093 |
| N2AB | 18812 | 56659;56660;56661 | chr2:178590368;178590367;178590366 | chr2:179455095;179455094;179455093 |
| N2A | 17885 | 53878;53879;53880 | chr2:178590368;178590367;178590366 | chr2:179455095;179455094;179455093 |
| N2B | 11388 | 34387;34388;34389 | chr2:178590368;178590367;178590366 | chr2:179455095;179455094;179455093 |
| Novex-1 | 11513 | 34762;34763;34764 | chr2:178590368;178590367;178590366 | chr2:179455095;179455094;179455093 |
| Novex-2 | 11580 | 34963;34964;34965 | chr2:178590368;178590367;178590366 | chr2:179455095;179455094;179455093 |
| 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 | rs962106912  |
None | 0.046 | N | 0.26 | 0.119 | 0.325533332567 | gnomAD-2.1.1 | 4.49E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 9.68E-06 | 0 |
| V/I | rs962106912 |
None | 0.046 | N | 0.26 | 0.119 | 0.325533332567 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| V/I | rs962106912 |
None | 0.046 | N | 0.26 | 0.119 | 0.325533332567 | gnomAD-4.0.0 | 1.89636E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.57565E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.2029 | likely_benign | 0.2083 | benign | -0.461 | Destabilizing | 0.939 | D | 0.48 | neutral | N | 0.437748504 | None | None | I |
| V/C | 0.7943 | likely_pathogenic | 0.7976 | pathogenic | -0.723 | Destabilizing | 0.999 | D | 0.707 | prob.neutral | None | None | None | None | I |
| V/D | 0.8304 | likely_pathogenic | 0.8809 | pathogenic | -0.244 | Destabilizing | 0.998 | D | 0.809 | deleterious | None | None | None | None | I |
| V/E | 0.6884 | likely_pathogenic | 0.75 | pathogenic | -0.353 | Destabilizing | 0.997 | D | 0.77 | deleterious | N | 0.469367322 | None | None | I |
| V/F | 0.3433 | ambiguous | 0.399 | ambiguous | -0.668 | Destabilizing | 0.986 | D | 0.691 | prob.neutral | None | None | None | None | I |
| V/G | 0.4712 | ambiguous | 0.5446 | ambiguous | -0.578 | Destabilizing | 0.997 | D | 0.783 | deleterious | N | 0.476266629 | None | None | I |
| V/H | 0.8532 | likely_pathogenic | 0.8899 | pathogenic | -0.049 | Destabilizing | 0.999 | D | 0.827 | deleterious | None | None | None | None | I |
| V/I | 0.0967 | likely_benign | 0.0987 | benign | -0.3 | Destabilizing | 0.046 | N | 0.26 | neutral | N | 0.46947692 | None | None | I |
| V/K | 0.774 | likely_pathogenic | 0.836 | pathogenic | -0.42 | Destabilizing | 0.993 | D | 0.781 | deleterious | None | None | None | None | I |
| V/L | 0.3852 | ambiguous | 0.4471 | ambiguous | -0.3 | Destabilizing | 0.76 | D | 0.513 | neutral | D | 0.523868766 | None | None | I |
| V/M | 0.2864 | likely_benign | 0.3469 | ambiguous | -0.463 | Destabilizing | 0.986 | D | 0.689 | prob.neutral | None | None | None | None | I |
| V/N | 0.6949 | likely_pathogenic | 0.7364 | pathogenic | -0.207 | Destabilizing | 0.998 | D | 0.814 | deleterious | None | None | None | None | I |
| V/P | 0.924 | likely_pathogenic | 0.9325 | pathogenic | -0.32 | Destabilizing | 0.998 | D | 0.795 | deleterious | None | None | None | None | I |
| V/Q | 0.6604 | likely_pathogenic | 0.7432 | pathogenic | -0.436 | Destabilizing | 0.998 | D | 0.796 | deleterious | None | None | None | None | I |
| V/R | 0.6612 | likely_pathogenic | 0.7343 | pathogenic | 0.104 | Stabilizing | 0.998 | D | 0.812 | deleterious | None | None | None | None | I |
| V/S | 0.3953 | ambiguous | 0.4282 | ambiguous | -0.575 | Destabilizing | 0.993 | D | 0.764 | deleterious | None | None | None | None | I |
| V/T | 0.2916 | likely_benign | 0.3098 | benign | -0.583 | Destabilizing | 0.953 | D | 0.64 | neutral | None | None | None | None | I |
| V/W | 0.9346 | likely_pathogenic | 0.953 | pathogenic | -0.725 | Destabilizing | 0.999 | D | 0.834 | deleterious | None | None | None | None | I |
| V/Y | 0.824 | likely_pathogenic | 0.852 | pathogenic | -0.441 | Destabilizing | 0.998 | D | 0.704 | prob.neutral | None | None | None | None | I |
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.