Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25305 | 76138;76139;76140 | chr2:178570219;178570218;178570217 | chr2:179434946;179434945;179434944 |
| N2AB | 23664 | 71215;71216;71217 | chr2:178570219;178570218;178570217 | chr2:179434946;179434945;179434944 |
| N2A | 22737 | 68434;68435;68436 | chr2:178570219;178570218;178570217 | chr2:179434946;179434945;179434944 |
| N2B | 16240 | 48943;48944;48945 | chr2:178570219;178570218;178570217 | chr2:179434946;179434945;179434944 |
| Novex-1 | 16365 | 49318;49319;49320 | chr2:178570219;178570218;178570217 | chr2:179434946;179434945;179434944 |
| Novex-2 | 16432 | 49519;49520;49521 | chr2:178570219;178570218;178570217 | chr2:179434946;179434945;179434944 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/L | rs142453163  |
-0.257 | 0.027 | D | 0.622 | 0.475 | None | gnomAD-2.1.1 | 9.66E-05 | None | None | None | None | N | None | 0 | 8.5E-05 | None | 0 | 0 | None | 0 | None | 0 | 1.88156E-04 | 0 |
| P/L | rs142453163 |
-0.257 | 0.027 | D | 0.622 | 0.475 | None | gnomAD-3.1.2 | 1.11857E-04 | None | None | None | None | N | None | 2.42E-05 | 2.62467E-04 | 0 | 0 | 0 | None | 0 | 0 | 1.76507E-04 | 0 | 0 |
| P/L | rs142453163 |
-0.257 | 0.027 | D | 0.622 | 0.475 | None | gnomAD-4.0.0 | 1.20247E-04 | None | None | None | None | N | None | 1.33422E-05 | 1.50115E-04 | None | 0 | 0 | None | 0 | 0 | 1.54288E-04 | 0 | 3.20195E-05 |
| P/S | rs1005621705 |
-2.146 | 0.256 | D | 0.458 | 0.531 | 0.380394304726 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.92E-06 | 0 |
| P/S | rs1005621705 |
-2.146 | 0.256 | D | 0.458 | 0.531 | 0.380394304726 | gnomAD-4.0.0 | 1.16339E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.52929E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.5185 | ambiguous | 0.5302 | ambiguous | -1.158 | Destabilizing | 0.657 | D | 0.582 | neutral | D | 0.537973951 | None | None | N |
| P/C | 0.9607 | likely_pathogenic | 0.962 | pathogenic | -2.099 | Highly Destabilizing | 0.998 | D | 0.774 | deleterious | None | None | None | None | N |
| P/D | 0.9988 | likely_pathogenic | 0.9986 | pathogenic | -3.421 | Highly Destabilizing | 0.947 | D | 0.671 | prob.neutral | None | None | None | None | N |
| P/E | 0.9959 | likely_pathogenic | 0.9953 | pathogenic | -3.359 | Highly Destabilizing | 0.947 | D | 0.693 | prob.delet. | None | None | None | None | N |
| P/F | 0.9989 | likely_pathogenic | 0.9988 | pathogenic | -0.877 | Destabilizing | 0.947 | D | 0.769 | deleterious | None | None | None | None | N |
| P/G | 0.9673 | likely_pathogenic | 0.9644 | pathogenic | -1.447 | Destabilizing | 0.835 | D | 0.665 | prob.neutral | None | None | None | None | N |
| P/H | 0.9943 | likely_pathogenic | 0.9939 | pathogenic | -0.939 | Destabilizing | 0.998 | D | 0.701 | prob.delet. | None | None | None | None | N |
| P/I | 0.989 | likely_pathogenic | 0.9889 | pathogenic | -0.423 | Destabilizing | 0.899 | D | 0.757 | deleterious | None | None | None | None | N |
| P/K | 0.9978 | likely_pathogenic | 0.9974 | pathogenic | -1.406 | Destabilizing | 0.947 | D | 0.699 | prob.delet. | None | None | None | None | N |
| P/L | 0.9443 | likely_pathogenic | 0.937 | pathogenic | -0.423 | Destabilizing | 0.027 | N | 0.622 | neutral | D | 0.540327354 | None | None | N |
| P/M | 0.99 | likely_pathogenic | 0.9903 | pathogenic | -0.836 | Destabilizing | 0.985 | D | 0.701 | prob.delet. | None | None | None | None | N |
| P/N | 0.9977 | likely_pathogenic | 0.9976 | pathogenic | -1.868 | Destabilizing | 0.947 | D | 0.713 | prob.delet. | None | None | None | None | N |
| P/Q | 0.9894 | likely_pathogenic | 0.989 | pathogenic | -2.021 | Highly Destabilizing | 0.964 | D | 0.645 | neutral | D | 0.565232465 | None | None | N |
| P/R | 0.9917 | likely_pathogenic | 0.9895 | pathogenic | -0.984 | Destabilizing | 0.964 | D | 0.689 | prob.delet. | D | 0.55362267 | None | None | N |
| P/S | 0.8783 | likely_pathogenic | 0.8939 | pathogenic | -2.08 | Highly Destabilizing | 0.256 | N | 0.458 | neutral | D | 0.553369181 | None | None | N |
| P/T | 0.9281 | likely_pathogenic | 0.9152 | pathogenic | -1.921 | Destabilizing | 0.792 | D | 0.631 | neutral | D | 0.553115691 | None | None | N |
| P/V | 0.9584 | likely_pathogenic | 0.9591 | pathogenic | -0.641 | Destabilizing | 0.717 | D | 0.695 | prob.delet. | None | None | None | None | N |
| P/W | 0.9995 | likely_pathogenic | 0.9993 | pathogenic | -1.259 | Destabilizing | 0.998 | D | 0.733 | deleterious | None | None | None | None | N |
| P/Y | 0.9991 | likely_pathogenic | 0.999 | pathogenic | -0.869 | Destabilizing | 0.973 | D | 0.768 | 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.