Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29824 | 89695;89696;89697 | chr2:178553535;178553534;178553533 | chr2:179418262;179418261;179418260 |
| N2AB | 28183 | 84772;84773;84774 | chr2:178553535;178553534;178553533 | chr2:179418262;179418261;179418260 |
| N2A | 27256 | 81991;81992;81993 | chr2:178553535;178553534;178553533 | chr2:179418262;179418261;179418260 |
| N2B | 20759 | 62500;62501;62502 | chr2:178553535;178553534;178553533 | chr2:179418262;179418261;179418260 |
| Novex-1 | 20884 | 62875;62876;62877 | chr2:178553535;178553534;178553533 | chr2:179418262;179418261;179418260 |
| Novex-2 | 20951 | 63076;63077;63078 | chr2:178553535;178553534;178553533 | chr2:179418262;179418261;179418260 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/R | rs764161774  |
-1.388 | 0.991 | N | 0.756 | 0.388 | 0.635979805963 | gnomAD-2.1.1 | 8.06E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.78E-05 | 0 |
| M/R | rs764161774 |
-1.388 | 0.991 | N | 0.756 | 0.388 | 0.635979805963 | gnomAD-4.0.0 | 8.2129E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.07953E-05 | 0 | 0 |
| M/T | None | None | 0.915 | N | 0.686 | 0.334 | 0.662284845153 | gnomAD-4.0.0 | 6.84408E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.87448E-05 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.6236 | likely_pathogenic | 0.657 | pathogenic | -2.281 | Highly Destabilizing | 0.745 | D | 0.628 | neutral | None | None | None | None | N |
| M/C | 0.7155 | likely_pathogenic | 0.7569 | pathogenic | -1.648 | Destabilizing | 0.998 | D | 0.625 | neutral | None | None | None | None | N |
| M/D | 0.9006 | likely_pathogenic | 0.9173 | pathogenic | -1.412 | Destabilizing | 0.994 | D | 0.761 | deleterious | None | None | None | None | N |
| M/E | 0.7234 | likely_pathogenic | 0.7437 | pathogenic | -1.255 | Destabilizing | 0.994 | D | 0.716 | prob.delet. | None | None | None | None | N |
| M/F | 0.4528 | ambiguous | 0.4763 | ambiguous | -0.829 | Destabilizing | 0.935 | D | 0.717 | prob.delet. | None | None | None | None | N |
| M/G | 0.7602 | likely_pathogenic | 0.7907 | pathogenic | -2.705 | Highly Destabilizing | 0.978 | D | 0.727 | deleterious | None | None | None | None | N |
| M/H | 0.7812 | likely_pathogenic | 0.8131 | pathogenic | -1.968 | Destabilizing | 0.998 | D | 0.647 | neutral | None | None | None | None | N |
| M/I | 0.4181 | ambiguous | 0.4055 | ambiguous | -1.093 | Destabilizing | 0.029 | N | 0.256 | neutral | N | 0.401758779 | None | None | N |
| M/K | 0.529 | ambiguous | 0.5385 | ambiguous | -1.275 | Destabilizing | 0.971 | D | 0.719 | prob.delet. | N | 0.507310164 | None | None | N |
| M/L | 0.162 | likely_benign | 0.1633 | benign | -1.093 | Destabilizing | 0.172 | N | 0.503 | neutral | N | 0.39230979 | None | None | N |
| M/N | 0.64 | likely_pathogenic | 0.6688 | pathogenic | -1.38 | Destabilizing | 0.994 | D | 0.71 | prob.delet. | None | None | None | None | N |
| M/P | 0.9325 | likely_pathogenic | 0.933 | pathogenic | -1.469 | Destabilizing | 0.994 | D | 0.705 | prob.delet. | None | None | None | None | N |
| M/Q | 0.4873 | ambiguous | 0.5278 | ambiguous | -1.24 | Destabilizing | 0.994 | D | 0.719 | prob.delet. | None | None | None | None | N |
| M/R | 0.5605 | ambiguous | 0.5768 | pathogenic | -1.041 | Destabilizing | 0.991 | D | 0.756 | deleterious | N | 0.499672115 | None | None | N |
| M/S | 0.6333 | likely_pathogenic | 0.6785 | pathogenic | -2.008 | Highly Destabilizing | 0.978 | D | 0.693 | prob.delet. | None | None | None | None | N |
| M/T | 0.4178 | ambiguous | 0.4424 | ambiguous | -1.736 | Destabilizing | 0.915 | D | 0.686 | prob.delet. | N | 0.399950625 | None | None | N |
| M/V | 0.1818 | likely_benign | 0.1787 | benign | -1.469 | Destabilizing | 0.325 | N | 0.469 | neutral | N | 0.424288922 | None | None | N |
| M/W | 0.7563 | likely_pathogenic | 0.7657 | pathogenic | -0.967 | Destabilizing | 0.998 | D | 0.654 | prob.neutral | None | None | None | None | N |
| M/Y | 0.7234 | likely_pathogenic | 0.7457 | pathogenic | -1.012 | Destabilizing | 0.994 | D | 0.754 | 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.