Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31656 | 95191;95192;95193 | chr2:178546365;178546364;178546363 | chr2:179411092;179411091;179411090 |
| N2AB | 30015 | 90268;90269;90270 | chr2:178546365;178546364;178546363 | chr2:179411092;179411091;179411090 |
| N2A | 29088 | 87487;87488;87489 | chr2:178546365;178546364;178546363 | chr2:179411092;179411091;179411090 |
| N2B | 22591 | 67996;67997;67998 | chr2:178546365;178546364;178546363 | chr2:179411092;179411091;179411090 |
| Novex-1 | 22716 | 68371;68372;68373 | chr2:178546365;178546364;178546363 | chr2:179411092;179411091;179411090 |
| Novex-2 | 22783 | 68572;68573;68574 | chr2:178546365;178546364;178546363 | chr2:179411092;179411091;179411090 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/I | rs748010504  |
-0.645 | 0.999 | N | 0.49 | 0.379 | 0.421799068777 | 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 |
| L/I | rs748010504 |
-0.645 | 0.999 | N | 0.49 | 0.379 | 0.421799068777 | gnomAD-4.0.0 | 6.84219E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.15937E-05 | 0 |
| L/V | rs748010504 |
None | 0.999 | N | 0.503 | 0.444 | 0.462461958149 | gnomAD-4.0.0 | 6.84219E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.9948E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.8559 | likely_pathogenic | 0.8602 | pathogenic | -2.369 | Highly Destabilizing | 0.999 | D | 0.673 | neutral | None | None | None | None | N |
| L/C | 0.9336 | likely_pathogenic | 0.9331 | pathogenic | -1.511 | Destabilizing | 1.0 | D | 0.745 | deleterious | None | None | None | None | N |
| L/D | 0.993 | likely_pathogenic | 0.9931 | pathogenic | -2.213 | Highly Destabilizing | 1.0 | D | 0.826 | deleterious | None | None | None | None | N |
| L/E | 0.9675 | likely_pathogenic | 0.9657 | pathogenic | -2.088 | Highly Destabilizing | 1.0 | D | 0.852 | deleterious | None | None | None | None | N |
| L/F | 0.4068 | ambiguous | 0.4376 | ambiguous | -1.482 | Destabilizing | 1.0 | D | 0.715 | prob.delet. | None | None | None | None | N |
| L/G | 0.9711 | likely_pathogenic | 0.9723 | pathogenic | -2.828 | Highly Destabilizing | 1.0 | D | 0.859 | deleterious | None | None | None | None | N |
| L/H | 0.9529 | likely_pathogenic | 0.9519 | pathogenic | -2.017 | Highly Destabilizing | 1.0 | D | 0.818 | deleterious | None | None | None | None | N |
| L/I | 0.139 | likely_benign | 0.1437 | benign | -1.093 | Destabilizing | 0.999 | D | 0.49 | neutral | N | 0.460180726 | None | None | N |
| L/K | 0.9522 | likely_pathogenic | 0.9465 | pathogenic | -1.859 | Destabilizing | 1.0 | D | 0.835 | deleterious | None | None | None | None | N |
| L/M | 0.1887 | likely_benign | 0.1937 | benign | -0.848 | Destabilizing | 1.0 | D | 0.721 | prob.delet. | None | None | None | None | N |
| L/N | 0.9785 | likely_pathogenic | 0.9786 | pathogenic | -1.879 | Destabilizing | 1.0 | D | 0.832 | deleterious | None | None | None | None | N |
| L/P | 0.9321 | likely_pathogenic | 0.9447 | pathogenic | -1.494 | Destabilizing | 1.0 | D | 0.835 | deleterious | N | 0.514710314 | None | None | N |
| L/Q | 0.917 | likely_pathogenic | 0.9134 | pathogenic | -1.913 | Destabilizing | 1.0 | D | 0.821 | deleterious | N | 0.511836705 | None | None | N |
| L/R | 0.9319 | likely_pathogenic | 0.9269 | pathogenic | -1.323 | Destabilizing | 1.0 | D | 0.839 | deleterious | D | 0.541043776 | None | None | N |
| L/S | 0.9731 | likely_pathogenic | 0.9752 | pathogenic | -2.555 | Highly Destabilizing | 1.0 | D | 0.828 | deleterious | None | None | None | None | N |
| L/T | 0.855 | likely_pathogenic | 0.8556 | pathogenic | -2.294 | Highly Destabilizing | 1.0 | D | 0.808 | deleterious | None | None | None | None | N |
| L/V | 0.2286 | likely_benign | 0.2276 | benign | -1.494 | Destabilizing | 0.999 | D | 0.503 | neutral | N | 0.467224128 | None | None | N |
| L/W | 0.7252 | likely_pathogenic | 0.7193 | pathogenic | -1.691 | Destabilizing | 1.0 | D | 0.763 | deleterious | None | None | None | None | N |
| L/Y | 0.8701 | likely_pathogenic | 0.8711 | pathogenic | -1.471 | Destabilizing | 1.0 | D | 0.811 | 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.