Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1367 | 4324;4325;4326 | chr2:178778983;178778982;178778981 | chr2:179643710;179643709;179643708 |
| N2AB | 1367 | 4324;4325;4326 | chr2:178778983;178778982;178778981 | chr2:179643710;179643709;179643708 |
| N2A | 1367 | 4324;4325;4326 | chr2:178778983;178778982;178778981 | chr2:179643710;179643709;179643708 |
| N2B | 1321 | 4186;4187;4188 | chr2:178778983;178778982;178778981 | chr2:179643710;179643709;179643708 |
| Novex-1 | 1321 | 4186;4187;4188 | chr2:178778983;178778982;178778981 | chr2:179643710;179643709;179643708 |
| Novex-2 | 1321 | 4186;4187;4188 | chr2:178778983;178778982;178778981 | chr2:179643710;179643709;179643708 |
| Novex-3 | 1367 | 4324;4325;4326 | chr2:178778983;178778982;178778981 | chr2:179643710;179643709;179643708 |
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/N | rs1015028448  |
None | 0.99 | N | 0.628 | 0.247 | 0.296679040009 | gnomAD-4.0.0 | 2.05239E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.69802E-06 | 0 | 0 |
| S/R | rs1307238681 |
None | 0.997 | N | 0.631 | 0.435 | 0.432936702747 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| S/R | rs1307238681 |
None | 0.997 | N | 0.631 | 0.435 | 0.432936702747 | gnomAD-4.0.0 | 9.29453E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.27123E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.1762 | likely_benign | 0.1695 | benign | -0.8 | Destabilizing | 0.469 | N | 0.251 | neutral | None | None | None | None | I |
| S/C | 0.2894 | likely_benign | 0.2969 | benign | -0.677 | Destabilizing | 1.0 | D | 0.64 | neutral | N | 0.514223191 | None | None | I |
| S/D | 0.9728 | likely_pathogenic | 0.9762 | pathogenic | -0.9 | Destabilizing | 0.993 | D | 0.601 | neutral | None | None | None | None | I |
| S/E | 0.9534 | likely_pathogenic | 0.9617 | pathogenic | -0.915 | Destabilizing | 0.993 | D | 0.605 | neutral | None | None | None | None | I |
| S/F | 0.8514 | likely_pathogenic | 0.8647 | pathogenic | -1.226 | Destabilizing | 0.999 | D | 0.733 | prob.delet. | None | None | None | None | I |
| S/G | 0.3483 | ambiguous | 0.3413 | ambiguous | -1.0 | Destabilizing | 0.98 | D | 0.579 | neutral | N | 0.513593341 | None | None | I |
| S/H | 0.8731 | likely_pathogenic | 0.8956 | pathogenic | -1.545 | Destabilizing | 1.0 | D | 0.638 | neutral | None | None | None | None | I |
| S/I | 0.7804 | likely_pathogenic | 0.7946 | pathogenic | -0.373 | Destabilizing | 0.994 | D | 0.71 | prob.delet. | N | 0.515160847 | None | None | I |
| S/K | 0.9878 | likely_pathogenic | 0.9895 | pathogenic | -0.737 | Destabilizing | 0.993 | D | 0.605 | neutral | None | None | None | None | I |
| S/L | 0.5478 | ambiguous | 0.5487 | ambiguous | -0.373 | Destabilizing | 0.985 | D | 0.685 | prob.neutral | None | None | None | None | I |
| S/M | 0.6199 | likely_pathogenic | 0.6427 | pathogenic | 0.091 | Stabilizing | 1.0 | D | 0.641 | neutral | None | None | None | None | I |
| S/N | 0.72 | likely_pathogenic | 0.7192 | pathogenic | -0.793 | Destabilizing | 0.99 | D | 0.628 | neutral | N | 0.511506893 | None | None | I |
| S/P | 0.9941 | likely_pathogenic | 0.9927 | pathogenic | -0.485 | Destabilizing | 0.998 | D | 0.626 | neutral | None | None | None | None | I |
| S/Q | 0.8943 | likely_pathogenic | 0.9137 | pathogenic | -1.078 | Destabilizing | 0.999 | D | 0.613 | neutral | None | None | None | None | I |
| S/R | 0.9734 | likely_pathogenic | 0.9774 | pathogenic | -0.522 | Destabilizing | 0.997 | D | 0.631 | neutral | N | 0.495261013 | None | None | I |
| S/T | 0.2024 | likely_benign | 0.202 | benign | -0.771 | Destabilizing | 0.4 | N | 0.306 | neutral | N | 0.439445554 | None | None | I |
| S/V | 0.6221 | likely_pathogenic | 0.6371 | pathogenic | -0.485 | Destabilizing | 0.985 | D | 0.678 | prob.neutral | None | None | None | None | I |
| S/W | 0.8981 | likely_pathogenic | 0.9108 | pathogenic | -1.198 | Destabilizing | 1.0 | D | 0.754 | deleterious | None | None | None | None | I |
| S/Y | 0.7812 | likely_pathogenic | 0.8076 | pathogenic | -0.906 | Destabilizing | 0.999 | D | 0.729 | prob.delet. | None | None | None | None | I |
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.