Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20088 | 60487;60488;60489 | chr2:178591463;178591462;178591461 | chr2:179456190;179456189;179456188 |
| N2AB | 18447 | 55564;55565;55566 | chr2:178591463;178591462;178591461 | chr2:179456190;179456189;179456188 |
| N2A | 17520 | 52783;52784;52785 | chr2:178591463;178591462;178591461 | chr2:179456190;179456189;179456188 |
| N2B | 11023 | 33292;33293;33294 | chr2:178591463;178591462;178591461 | chr2:179456190;179456189;179456188 |
| Novex-1 | 11148 | 33667;33668;33669 | chr2:178591463;178591462;178591461 | chr2:179456190;179456189;179456188 |
| Novex-2 | 11215 | 33868;33869;33870 | chr2:178591463;178591462;178591461 | chr2:179456190;179456189;179456188 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/H | rs747560869  |
-1.241 | 1.0 | N | 0.711 | 0.569 | 0.901459665828 | gnomAD-2.1.1 | 4.4E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 9.39E-06 | 0 |
| L/H | rs747560869 |
-1.241 | 1.0 | N | 0.711 | 0.569 | 0.901459665828 | gnomAD-4.0.0 | 6.95384E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.05984E-07 | 0 | 0 |
| L/P | rs747560869 |
None | 0.999 | D | 0.725 | 0.657 | 0.908644682553 | 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 |
| L/P | rs747560869 |
None | 0.999 | D | 0.725 | 0.657 | 0.908644682553 | gnomAD-4.0.0 | 2.51552E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.41367E-06 | 0 | 0 |
| L/V | rs769097181 |
-0.862 | 0.9 | N | 0.281 | 0.22 | 0.648878273322 | gnomAD-2.1.1 | 2.65E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 2.36165E-04 | None | 0 | 0 | 0 |
| L/V | rs769097181 |
-0.862 | 0.9 | N | 0.281 | 0.22 | 0.648878273322 | gnomAD-4.0.0 | 1.80914E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 3.19819E-04 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.7346 | likely_pathogenic | 0.7192 | pathogenic | -1.737 | Destabilizing | 0.983 | D | 0.468 | neutral | None | None | None | None | N |
| L/C | 0.8608 | likely_pathogenic | 0.8388 | pathogenic | -1.379 | Destabilizing | 1.0 | D | 0.62 | neutral | None | None | None | None | N |
| L/D | 0.9777 | likely_pathogenic | 0.9724 | pathogenic | -0.891 | Destabilizing | 0.999 | D | 0.733 | prob.delet. | None | None | None | None | N |
| L/E | 0.8788 | likely_pathogenic | 0.8663 | pathogenic | -0.77 | Destabilizing | 0.999 | D | 0.725 | prob.delet. | None | None | None | None | N |
| L/F | 0.3987 | ambiguous | 0.3513 | ambiguous | -0.888 | Destabilizing | 0.997 | D | 0.537 | neutral | N | 0.486683969 | None | None | N |
| L/G | 0.956 | likely_pathogenic | 0.9524 | pathogenic | -2.162 | Highly Destabilizing | 0.999 | D | 0.724 | prob.delet. | None | None | None | None | N |
| L/H | 0.762 | likely_pathogenic | 0.7121 | pathogenic | -1.198 | Destabilizing | 1.0 | D | 0.711 | prob.delet. | N | 0.509093865 | None | None | N |
| L/I | 0.1191 | likely_benign | 0.112 | benign | -0.59 | Destabilizing | 0.37 | N | 0.152 | neutral | N | 0.454097328 | None | None | N |
| L/K | 0.7325 | likely_pathogenic | 0.6966 | pathogenic | -1.25 | Destabilizing | 0.999 | D | 0.693 | prob.neutral | None | None | None | None | N |
| L/M | 0.162 | likely_benign | 0.1533 | benign | -0.72 | Destabilizing | 0.998 | D | 0.567 | neutral | None | None | None | None | N |
| L/N | 0.8807 | likely_pathogenic | 0.8665 | pathogenic | -1.355 | Destabilizing | 0.999 | D | 0.725 | prob.delet. | None | None | None | None | N |
| L/P | 0.9659 | likely_pathogenic | 0.9629 | pathogenic | -0.944 | Destabilizing | 0.999 | D | 0.725 | prob.delet. | D | 0.52719812 | None | None | N |
| L/Q | 0.619 | likely_pathogenic | 0.5862 | pathogenic | -1.307 | Destabilizing | 0.999 | D | 0.686 | prob.neutral | None | None | None | None | N |
| L/R | 0.6983 | likely_pathogenic | 0.6739 | pathogenic | -0.873 | Destabilizing | 0.999 | D | 0.705 | prob.neutral | D | 0.530867388 | None | None | N |
| L/S | 0.8852 | likely_pathogenic | 0.872 | pathogenic | -2.115 | Highly Destabilizing | 0.999 | D | 0.67 | neutral | None | None | None | None | N |
| L/T | 0.6725 | likely_pathogenic | 0.6679 | pathogenic | -1.843 | Destabilizing | 0.998 | D | 0.601 | neutral | None | None | None | None | N |
| L/V | 0.1604 | likely_benign | 0.1527 | benign | -0.944 | Destabilizing | 0.9 | D | 0.281 | neutral | N | 0.453862468 | None | None | N |
| L/W | 0.6771 | likely_pathogenic | 0.6391 | pathogenic | -0.989 | Destabilizing | 1.0 | D | 0.675 | neutral | None | None | None | None | N |
| L/Y | 0.763 | likely_pathogenic | 0.7249 | pathogenic | -0.756 | Destabilizing | 0.999 | D | 0.657 | neutral | 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.