Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15955 | 48088;48089;48090 | chr2:178617132;178617131;178617130 | chr2:179481859;179481858;179481857 |
| N2AB | 14314 | 43165;43166;43167 | chr2:178617132;178617131;178617130 | chr2:179481859;179481858;179481857 |
| N2A | 13387 | 40384;40385;40386 | chr2:178617132;178617131;178617130 | chr2:179481859;179481858;179481857 |
| N2B | 6890 | 20893;20894;20895 | chr2:178617132;178617131;178617130 | chr2:179481859;179481858;179481857 |
| Novex-1 | 7015 | 21268;21269;21270 | chr2:178617132;178617131;178617130 | chr2:179481859;179481858;179481857 |
| Novex-2 | 7082 | 21469;21470;21471 | chr2:178617132;178617131;178617130 | chr2:179481859;179481858;179481857 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/E | None | None | 1.0 | N | 0.443 | 0.206 | 0.107399877778 | gnomAD-4.0.0 | 1.37179E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.00846E-07 | 0 | 1.66157E-05 |
| D/H | rs1363215463  |
-0.736 | 1.0 | N | 0.79 | 0.389 | 0.207176502487 | gnomAD-2.1.1 | 4.1E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 9.1E-06 | 0 |
| D/H | rs1363215463 |
-0.736 | 1.0 | N | 0.79 | 0.389 | 0.207176502487 | 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 |
| D/H | rs1363215463 |
-0.736 | 1.0 | N | 0.79 | 0.389 | 0.207176502487 | gnomAD-4.0.0 | 2.57433E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.80568E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.2628 | likely_benign | 0.2594 | benign | 0.265 | Stabilizing | 1.0 | D | 0.737 | deleterious | N | 0.454663573 | None | None | N |
| D/C | 0.7455 | likely_pathogenic | 0.7255 | pathogenic | 0.488 | Stabilizing | 1.0 | D | 0.763 | deleterious | None | None | None | None | N |
| D/E | 0.2499 | likely_benign | 0.2334 | benign | -0.598 | Destabilizing | 1.0 | D | 0.443 | neutral | N | 0.440907319 | None | None | N |
| D/F | 0.7781 | likely_pathogenic | 0.7692 | pathogenic | -0.419 | Destabilizing | 1.0 | D | 0.807 | deleterious | None | None | None | None | N |
| D/G | 0.2701 | likely_benign | 0.2557 | benign | 0.074 | Stabilizing | 1.0 | D | 0.693 | prob.delet. | N | 0.448500794 | None | None | N |
| D/H | 0.4749 | ambiguous | 0.4583 | ambiguous | -0.761 | Destabilizing | 1.0 | D | 0.79 | deleterious | N | 0.491867466 | None | None | N |
| D/I | 0.5767 | likely_pathogenic | 0.5627 | ambiguous | 0.7 | Stabilizing | 1.0 | D | 0.788 | deleterious | None | None | None | None | N |
| D/K | 0.4739 | ambiguous | 0.4455 | ambiguous | 0.365 | Stabilizing | 1.0 | D | 0.749 | deleterious | None | None | None | None | N |
| D/L | 0.5506 | ambiguous | 0.5491 | ambiguous | 0.7 | Stabilizing | 1.0 | D | 0.787 | deleterious | None | None | None | None | N |
| D/M | 0.7525 | likely_pathogenic | 0.7472 | pathogenic | 1.068 | Stabilizing | 1.0 | D | 0.749 | deleterious | None | None | None | None | N |
| D/N | 0.1374 | likely_benign | 0.1257 | benign | 0.267 | Stabilizing | 1.0 | D | 0.545 | neutral | N | 0.448006502 | None | None | N |
| D/P | 0.9326 | likely_pathogenic | 0.9348 | pathogenic | 0.58 | Stabilizing | 1.0 | D | 0.734 | deleterious | None | None | None | None | N |
| D/Q | 0.4827 | ambiguous | 0.4632 | ambiguous | 0.269 | Stabilizing | 1.0 | D | 0.731 | deleterious | None | None | None | None | N |
| D/R | 0.4959 | ambiguous | 0.4809 | ambiguous | 0.13 | Stabilizing | 1.0 | D | 0.8 | deleterious | None | None | None | None | N |
| D/S | 0.1675 | likely_benign | 0.1551 | benign | 0.179 | Stabilizing | 1.0 | D | 0.675 | prob.neutral | None | None | None | None | N |
| D/T | 0.3631 | ambiguous | 0.3444 | ambiguous | 0.317 | Stabilizing | 1.0 | D | 0.743 | deleterious | None | None | None | None | N |
| D/V | 0.3519 | ambiguous | 0.3466 | ambiguous | 0.58 | Stabilizing | 1.0 | D | 0.763 | deleterious | N | 0.458947794 | None | None | N |
| D/W | 0.9374 | likely_pathogenic | 0.9362 | pathogenic | -0.636 | Destabilizing | 1.0 | D | 0.764 | deleterious | None | None | None | None | N |
| D/Y | 0.4003 | ambiguous | 0.3989 | ambiguous | -0.258 | Destabilizing | 1.0 | D | 0.801 | deleterious | N | 0.443918776 | 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.