Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 35020 | 105283;105284;105285 | chr2:178531557;178531556;178531555 | chr2:179396284;179396283;179396282 |
| N2AB | 33379 | 100360;100361;100362 | chr2:178531557;178531556;178531555 | chr2:179396284;179396283;179396282 |
| N2A | 32452 | 97579;97580;97581 | chr2:178531557;178531556;178531555 | chr2:179396284;179396283;179396282 |
| N2B | 25955 | 78088;78089;78090 | chr2:178531557;178531556;178531555 | chr2:179396284;179396283;179396282 |
| Novex-1 | 26080 | 78463;78464;78465 | chr2:178531557;178531556;178531555 | chr2:179396284;179396283;179396282 |
| Novex-2 | 26147 | 78664;78665;78666 | chr2:178531557;178531556;178531555 | chr2:179396284;179396283;179396282 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/E | rs1689123371  |
None | 0.996 | N | 0.596 | 0.379 | 0.468834750356 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 1.92901E-04 | None | 0 | 0 | 0 | 0 | 0 |
| K/E | rs1689123371 |
None | 0.996 | N | 0.596 | 0.379 | 0.468834750356 | gnomAD-4.0.0 | 6.57263E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 1.92901E-04 | None | 0 | 0 | 0 | 0 | 0 |
| K/R | rs1178732521 |
None | 0.64 | N | 0.447 | 0.237 | 0.323342291347 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| K/R | rs1178732521 |
None | 0.64 | N | 0.447 | 0.237 | 0.323342291347 | gnomAD-4.0.0 | 6.57125E-06 | None | None | None | None | I | None | 2.41313E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| K/T | rs1178732521 |
-0.69 | 0.999 | N | 0.635 | 0.552 | 0.520427616228 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 6.46E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| K/T | rs1178732521 |
-0.69 | 0.999 | N | 0.635 | 0.552 | 0.520427616228 | gnomAD-4.0.0 | 1.59094E-06 | None | None | None | None | I | None | 5.65227E-05 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/A | 0.9241 | likely_pathogenic | 0.9561 | pathogenic | -0.168 | Destabilizing | 0.998 | D | 0.615 | neutral | None | None | None | None | I |
| K/C | 0.9605 | likely_pathogenic | 0.9743 | pathogenic | -0.476 | Destabilizing | 1.0 | D | 0.755 | deleterious | None | None | None | None | I |
| K/D | 0.9907 | likely_pathogenic | 0.9935 | pathogenic | -0.164 | Destabilizing | 1.0 | D | 0.672 | neutral | None | None | None | None | I |
| K/E | 0.9038 | likely_pathogenic | 0.9314 | pathogenic | -0.132 | Destabilizing | 0.996 | D | 0.596 | neutral | N | 0.490922133 | None | None | I |
| K/F | 0.9891 | likely_pathogenic | 0.9935 | pathogenic | -0.366 | Destabilizing | 1.0 | D | 0.715 | prob.delet. | None | None | None | None | I |
| K/G | 0.9695 | likely_pathogenic | 0.9813 | pathogenic | -0.366 | Destabilizing | 1.0 | D | 0.598 | neutral | None | None | None | None | I |
| K/H | 0.8193 | likely_pathogenic | 0.8725 | pathogenic | -0.517 | Destabilizing | 1.0 | D | 0.681 | prob.neutral | None | None | None | None | I |
| K/I | 0.9529 | likely_pathogenic | 0.9754 | pathogenic | 0.283 | Stabilizing | 1.0 | D | 0.72 | prob.delet. | None | None | None | None | I |
| K/L | 0.8916 | likely_pathogenic | 0.9258 | pathogenic | 0.283 | Stabilizing | 1.0 | D | 0.598 | neutral | None | None | None | None | I |
| K/M | 0.8435 | likely_pathogenic | 0.8938 | pathogenic | -0.136 | Destabilizing | 1.0 | D | 0.687 | prob.neutral | N | 0.501965846 | None | None | I |
| K/N | 0.9695 | likely_pathogenic | 0.9819 | pathogenic | -0.127 | Destabilizing | 0.999 | D | 0.69 | prob.neutral | N | 0.502312563 | None | None | I |
| K/P | 0.9929 | likely_pathogenic | 0.9946 | pathogenic | 0.159 | Stabilizing | 1.0 | D | 0.669 | neutral | None | None | None | None | I |
| K/Q | 0.6714 | likely_pathogenic | 0.7601 | pathogenic | -0.198 | Destabilizing | 0.999 | D | 0.691 | prob.neutral | N | 0.491095491 | None | None | I |
| K/R | 0.1788 | likely_benign | 0.2142 | benign | -0.161 | Destabilizing | 0.64 | D | 0.447 | neutral | N | 0.491095491 | None | None | I |
| K/S | 0.9644 | likely_pathogenic | 0.9797 | pathogenic | -0.535 | Destabilizing | 0.998 | D | 0.626 | neutral | None | None | None | None | I |
| K/T | 0.9058 | likely_pathogenic | 0.9285 | pathogenic | -0.351 | Destabilizing | 0.999 | D | 0.635 | neutral | N | 0.518818023 | None | None | I |
| K/V | 0.9252 | likely_pathogenic | 0.9584 | pathogenic | 0.159 | Stabilizing | 1.0 | D | 0.681 | prob.neutral | None | None | None | None | I |
| K/W | 0.9855 | likely_pathogenic | 0.9888 | pathogenic | -0.438 | Destabilizing | 1.0 | D | 0.761 | deleterious | None | None | None | None | I |
| K/Y | 0.966 | likely_pathogenic | 0.9791 | pathogenic | -0.094 | Destabilizing | 1.0 | D | 0.711 | prob.delet. | 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.