Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14521 | 43786;43787;43788 | chr2:178632333;178632332;178632331 | chr2:179497060;179497059;179497058 |
| N2AB | 12880 | 38863;38864;38865 | chr2:178632333;178632332;178632331 | chr2:179497060;179497059;179497058 |
| N2A | 11953 | 36082;36083;36084 | chr2:178632333;178632332;178632331 | chr2:179497060;179497059;179497058 |
| N2B | 5456 | 16591;16592;16593 | chr2:178632333;178632332;178632331 | chr2:179497060;179497059;179497058 |
| Novex-1 | 5581 | 16966;16967;16968 | chr2:178632333;178632332;178632331 | chr2:179497060;179497059;179497058 |
| Novex-2 | 5648 | 17167;17168;17169 | chr2:178632333;178632332;178632331 | chr2:179497060;179497059;179497058 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | None | None | 0.997 | D | 0.382 | 0.497 | 0.510524285738 | gnomAD-4.0.0 | 6.8753E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.177E-05 | 0 |
| S/C | rs1326450347  |
None | 1.0 | D | 0.699 | 0.559 | 0.666426553935 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| S/C | rs1326450347 |
None | 1.0 | D | 0.699 | 0.559 | 0.666426553935 | gnomAD-4.0.0 | 6.57903E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.47106E-05 | 0 | 0 |
| S/F | None | None | 1.0 | D | 0.741 | 0.535 | 0.648203075438 | gnomAD-4.0.0 | 1.37494E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.80453E-06 | 0 | 0 |
| S/P | rs1161247099 |
-0.127 | 1.0 | D | 0.689 | 0.626 | 0.593315388404 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | N | None | 1.14758E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| S/P | rs1161247099 |
-0.127 | 1.0 | D | 0.689 | 0.626 | 0.593315388404 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| S/P | rs1161247099 |
-0.127 | 1.0 | D | 0.689 | 0.626 | 0.593315388404 | gnomAD-4.0.0 | 3.73471E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.25082E-06 | 0 | 1.60767E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.5732 | likely_pathogenic | 0.6116 | pathogenic | -0.499 | Destabilizing | 0.997 | D | 0.382 | neutral | D | 0.677368833 | None | None | N |
| S/C | 0.7854 | likely_pathogenic | 0.8284 | pathogenic | -0.342 | Destabilizing | 1.0 | D | 0.699 | prob.neutral | D | 0.682805802 | None | None | N |
| S/D | 0.9227 | likely_pathogenic | 0.9163 | pathogenic | -0.136 | Destabilizing | 0.999 | D | 0.565 | neutral | None | None | None | None | N |
| S/E | 0.9798 | likely_pathogenic | 0.9813 | pathogenic | -0.09 | Destabilizing | 0.999 | D | 0.558 | neutral | None | None | None | None | N |
| S/F | 0.963 | likely_pathogenic | 0.9724 | pathogenic | -0.463 | Destabilizing | 1.0 | D | 0.741 | deleterious | D | 0.64322013 | None | None | N |
| S/G | 0.6152 | likely_pathogenic | 0.6373 | pathogenic | -0.804 | Destabilizing | 0.999 | D | 0.447 | neutral | None | None | None | None | N |
| S/H | 0.9613 | likely_pathogenic | 0.9664 | pathogenic | -1.175 | Destabilizing | 1.0 | D | 0.724 | prob.delet. | None | None | None | None | N |
| S/I | 0.9039 | likely_pathogenic | 0.9305 | pathogenic | 0.214 | Stabilizing | 1.0 | D | 0.701 | prob.neutral | None | None | None | None | N |
| S/K | 0.9975 | likely_pathogenic | 0.998 | pathogenic | -0.625 | Destabilizing | 0.999 | D | 0.559 | neutral | None | None | None | None | N |
| S/L | 0.7618 | likely_pathogenic | 0.818 | pathogenic | 0.214 | Stabilizing | 1.0 | D | 0.637 | neutral | None | None | None | None | N |
| S/M | 0.8856 | likely_pathogenic | 0.9152 | pathogenic | 0.25 | Stabilizing | 1.0 | D | 0.725 | prob.delet. | None | None | None | None | N |
| S/N | 0.6777 | likely_pathogenic | 0.714 | pathogenic | -0.688 | Destabilizing | 0.999 | D | 0.525 | neutral | None | None | None | None | N |
| S/P | 0.9726 | likely_pathogenic | 0.9822 | pathogenic | 0.012 | Stabilizing | 1.0 | D | 0.689 | prob.neutral | D | 0.619047235 | None | None | N |
| S/Q | 0.9794 | likely_pathogenic | 0.9833 | pathogenic | -0.674 | Destabilizing | 1.0 | D | 0.687 | prob.neutral | None | None | None | None | N |
| S/R | 0.9947 | likely_pathogenic | 0.996 | pathogenic | -0.631 | Destabilizing | 1.0 | D | 0.68 | prob.neutral | None | None | None | None | N |
| S/T | 0.3765 | ambiguous | 0.3975 | ambiguous | -0.632 | Destabilizing | 0.999 | D | 0.416 | neutral | N | 0.505199458 | None | None | N |
| S/V | 0.9244 | likely_pathogenic | 0.9416 | pathogenic | 0.012 | Stabilizing | 1.0 | D | 0.699 | prob.neutral | None | None | None | None | N |
| S/W | 0.9686 | likely_pathogenic | 0.975 | pathogenic | -0.553 | Destabilizing | 1.0 | D | 0.74 | deleterious | None | None | None | None | N |
| S/Y | 0.9279 | likely_pathogenic | 0.9427 | pathogenic | -0.244 | Destabilizing | 1.0 | D | 0.745 | deleterious | D | 0.681058906 | 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.