Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14966 | 45121;45122;45123 | chr2:178622687;178622686;178622685 | chr2:179487414;179487413;179487412 |
| N2AB | 13325 | 40198;40199;40200 | chr2:178622687;178622686;178622685 | chr2:179487414;179487413;179487412 |
| N2A | 12398 | 37417;37418;37419 | chr2:178622687;178622686;178622685 | chr2:179487414;179487413;179487412 |
| N2B | 5901 | 17926;17927;17928 | chr2:178622687;178622686;178622685 | chr2:179487414;179487413;179487412 |
| Novex-1 | 6026 | 18301;18302;18303 | chr2:178622687;178622686;178622685 | chr2:179487414;179487413;179487412 |
| Novex-2 | 6093 | 18502;18503;18504 | chr2:178622687;178622686;178622685 | chr2:179487414;179487413;179487412 |
| 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/C | rs1022414957  |
None | 1.0 | D | 0.704 | 0.583 | 0.758948374077 | gnomAD-3.1.2 | 6.59E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| S/C | rs1022414957 |
None | 1.0 | D | 0.704 | 0.583 | 0.758948374077 | gnomAD-4.0.0 | 6.59152E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.47406E-05 | 0 | 0 |
| S/P | rs760963803 |
-0.047 | 1.0 | D | 0.702 | 0.615 | 0.541962755691 | gnomAD-2.1.1 | 4.16E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.45E-05 | None | 0 | 0 | 0 |
| S/P | rs760963803 |
-0.047 | 1.0 | D | 0.702 | 0.615 | 0.541962755691 | gnomAD-4.0.0 | 1.60872E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.46319E-05 | 0 |
| S/Y | None | None | 1.0 | D | 0.767 | 0.577 | 0.863293222284 | gnomAD-4.0.0 | 6.87597E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.02247E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.3124 | likely_benign | 0.2889 | benign | -0.415 | Destabilizing | 0.997 | D | 0.36 | neutral | D | 0.531550939 | None | None | N |
| S/C | 0.6146 | likely_pathogenic | 0.5321 | ambiguous | -0.349 | Destabilizing | 1.0 | D | 0.704 | prob.neutral | D | 0.694235773 | None | None | N |
| S/D | 0.7763 | likely_pathogenic | 0.7222 | pathogenic | 0.29 | Stabilizing | 0.999 | D | 0.553 | neutral | None | None | None | None | N |
| S/E | 0.9078 | likely_pathogenic | 0.8856 | pathogenic | 0.26 | Stabilizing | 0.999 | D | 0.545 | neutral | None | None | None | None | N |
| S/F | 0.8235 | likely_pathogenic | 0.7655 | pathogenic | -0.624 | Destabilizing | 1.0 | D | 0.765 | deleterious | D | 0.654420079 | None | None | N |
| S/G | 0.2771 | likely_benign | 0.2501 | benign | -0.632 | Destabilizing | 0.999 | D | 0.434 | neutral | None | None | None | None | N |
| S/H | 0.8534 | likely_pathogenic | 0.8193 | pathogenic | -1.043 | Destabilizing | 1.0 | D | 0.729 | prob.delet. | None | None | None | None | N |
| S/I | 0.7047 | likely_pathogenic | 0.6293 | pathogenic | 0.043 | Stabilizing | 1.0 | D | 0.727 | prob.delet. | None | None | None | None | N |
| S/K | 0.9728 | likely_pathogenic | 0.9634 | pathogenic | -0.54 | Destabilizing | 0.999 | D | 0.547 | neutral | None | None | None | None | N |
| S/L | 0.4254 | ambiguous | 0.3692 | ambiguous | 0.043 | Stabilizing | 1.0 | D | 0.643 | neutral | None | None | None | None | N |
| S/M | 0.6896 | likely_pathogenic | 0.6491 | pathogenic | 0.095 | Stabilizing | 1.0 | D | 0.729 | prob.delet. | None | None | None | None | N |
| S/N | 0.4466 | ambiguous | 0.3951 | ambiguous | -0.361 | Destabilizing | 0.999 | D | 0.515 | neutral | None | None | None | None | N |
| S/P | 0.8014 | likely_pathogenic | 0.7183 | pathogenic | -0.076 | Destabilizing | 1.0 | D | 0.702 | prob.neutral | D | 0.601022718 | None | None | N |
| S/Q | 0.9031 | likely_pathogenic | 0.8921 | pathogenic | -0.497 | Destabilizing | 1.0 | D | 0.686 | prob.neutral | None | None | None | None | N |
| S/R | 0.9606 | likely_pathogenic | 0.9449 | pathogenic | -0.427 | Destabilizing | 1.0 | D | 0.694 | prob.neutral | None | None | None | None | N |
| S/T | 0.1917 | likely_benign | 0.1733 | benign | -0.437 | Destabilizing | 0.999 | D | 0.406 | neutral | N | 0.509348685 | None | None | N |
| S/V | 0.7141 | likely_pathogenic | 0.6458 | pathogenic | -0.076 | Destabilizing | 1.0 | D | 0.722 | prob.delet. | None | None | None | None | N |
| S/W | 0.8624 | likely_pathogenic | 0.8215 | pathogenic | -0.627 | Destabilizing | 1.0 | D | 0.752 | deleterious | None | None | None | None | N |
| S/Y | 0.7371 | likely_pathogenic | 0.6786 | pathogenic | -0.353 | Destabilizing | 1.0 | D | 0.767 | deleterious | D | 0.692499475 | 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.