Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15587 | 46984;46985;46986 | chr2:178618791;178618790;178618789 | chr2:179483518;179483517;179483516 |
| N2AB | 13946 | 42061;42062;42063 | chr2:178618791;178618790;178618789 | chr2:179483518;179483517;179483516 |
| N2A | 13019 | 39280;39281;39282 | chr2:178618791;178618790;178618789 | chr2:179483518;179483517;179483516 |
| N2B | 6522 | 19789;19790;19791 | chr2:178618791;178618790;178618789 | chr2:179483518;179483517;179483516 |
| Novex-1 | 6647 | 20164;20165;20166 | chr2:178618791;178618790;178618789 | chr2:179483518;179483517;179483516 |
| Novex-2 | 6714 | 20365;20366;20367 | chr2:178618791;178618790;178618789 | chr2:179483518;179483517;179483516 |
| 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/I | rs776451592  |
-0.37 | 0.985 | N | 0.685 | 0.357 | 0.584797538282 | gnomAD-2.1.1 | 8.1E-06 | None | None | None | None | N | None | 0 | 5.83E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| M/I | rs776451592 |
-0.37 | 0.985 | N | 0.685 | 0.357 | 0.584797538282 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.42E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| M/I | rs776451592 |
-0.37 | 0.985 | N | 0.685 | 0.357 | 0.584797538282 | gnomAD-4.0.0 | 1.24127E-06 | None | None | None | None | N | None | 2.67508E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| M/T | None | None | 0.994 | N | 0.748 | 0.622 | 0.852084556051 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 6.33473E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| M/V | rs761595575 |
-0.86 | 0.985 | N | 0.617 | 0.378 | 0.581977844477 | gnomAD-2.1.1 | 4.05E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.28E-05 | None | 0 | 0 | 0 |
| M/V | rs761595575 |
-0.86 | 0.985 | N | 0.617 | 0.378 | 0.581977844477 | gnomAD-4.0.0 | 3.42613E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.60085E-06 | 1.16098E-05 | 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 | 0.812 | likely_pathogenic | 0.8511 | pathogenic | -0.899 | Destabilizing | 0.989 | D | 0.724 | prob.delet. | None | None | None | None | N |
| M/C | 0.9096 | likely_pathogenic | 0.921 | pathogenic | -1.397 | Destabilizing | 1.0 | D | 0.772 | deleterious | None | None | None | None | N |
| M/D | 0.9988 | likely_pathogenic | 0.9984 | pathogenic | -1.295 | Destabilizing | 0.999 | D | 0.867 | deleterious | None | None | None | None | N |
| M/E | 0.9913 | likely_pathogenic | 0.9898 | pathogenic | -1.045 | Destabilizing | 0.999 | D | 0.831 | deleterious | None | None | None | None | N |
| M/F | 0.4288 | ambiguous | 0.4472 | ambiguous | -0.111 | Destabilizing | 0.999 | D | 0.743 | deleterious | None | None | None | None | N |
| M/G | 0.9727 | likely_pathogenic | 0.9747 | pathogenic | -1.342 | Destabilizing | 0.995 | D | 0.836 | deleterious | None | None | None | None | N |
| M/H | 0.9896 | likely_pathogenic | 0.9898 | pathogenic | -1.519 | Destabilizing | 1.0 | D | 0.847 | deleterious | None | None | None | None | N |
| M/I | 0.55 | ambiguous | 0.5623 | ambiguous | 0.378 | Stabilizing | 0.985 | D | 0.685 | prob.neutral | N | 0.494218281 | None | None | N |
| M/K | 0.9694 | likely_pathogenic | 0.9674 | pathogenic | -0.405 | Destabilizing | 0.994 | D | 0.759 | deleterious | N | 0.510833671 | None | None | N |
| M/L | 0.1873 | likely_benign | 0.2011 | benign | 0.378 | Stabilizing | 0.927 | D | 0.37 | neutral | N | 0.474541698 | None | None | N |
| M/N | 0.9925 | likely_pathogenic | 0.991 | pathogenic | -1.011 | Destabilizing | 0.999 | D | 0.838 | deleterious | None | None | None | None | N |
| M/P | 0.9948 | likely_pathogenic | 0.9942 | pathogenic | -0.032 | Destabilizing | 0.999 | D | 0.84 | deleterious | None | None | None | None | N |
| M/Q | 0.964 | likely_pathogenic | 0.9603 | pathogenic | -0.534 | Destabilizing | 0.999 | D | 0.754 | deleterious | None | None | None | None | N |
| M/R | 0.9649 | likely_pathogenic | 0.9647 | pathogenic | -1.043 | Destabilizing | 0.998 | D | 0.798 | deleterious | N | 0.510833671 | None | None | N |
| M/S | 0.9687 | likely_pathogenic | 0.9714 | pathogenic | -1.329 | Destabilizing | 0.995 | D | 0.736 | prob.delet. | None | None | None | None | N |
| M/T | 0.8916 | likely_pathogenic | 0.9109 | pathogenic | -0.937 | Destabilizing | 0.994 | D | 0.748 | deleterious | N | 0.510637139 | None | None | N |
| M/V | 0.1478 | likely_benign | 0.1616 | benign | -0.032 | Destabilizing | 0.985 | D | 0.617 | neutral | N | 0.504306026 | None | None | N |
| M/W | 0.9562 | likely_pathogenic | 0.9626 | pathogenic | -0.493 | Destabilizing | 1.0 | D | 0.769 | deleterious | None | None | None | None | N |
| M/Y | 0.9401 | likely_pathogenic | 0.9418 | pathogenic | -0.302 | Destabilizing | 0.999 | D | 0.793 | 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.