Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22004 | 66235;66236;66237 | chr2:178582446;178582445;178582444 | chr2:179447173;179447172;179447171 |
| N2AB | 20363 | 61312;61313;61314 | chr2:178582446;178582445;178582444 | chr2:179447173;179447172;179447171 |
| N2A | 19436 | 58531;58532;58533 | chr2:178582446;178582445;178582444 | chr2:179447173;179447172;179447171 |
| N2B | 12939 | 39040;39041;39042 | chr2:178582446;178582445;178582444 | chr2:179447173;179447172;179447171 |
| Novex-1 | 13064 | 39415;39416;39417 | chr2:178582446;178582445;178582444 | chr2:179447173;179447172;179447171 |
| Novex-2 | 13131 | 39616;39617;39618 | chr2:178582446;178582445;178582444 | chr2:179447173;179447172;179447171 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/D | rs1379206431  |
-1.056 | 0.988 | N | 0.729 | 0.434 | 0.442672919754 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 2.91E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| A/D | rs1379206431 |
-1.056 | 0.988 | N | 0.729 | 0.434 | 0.442672919754 | gnomAD-4.0.0 | 1.59316E-06 | None | None | None | None | N | None | 0 | 2.28864E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| A/T | None | None | 0.919 | N | 0.635 | 0.29 | 0.244539031024 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.79 | likely_pathogenic | 0.7646 | pathogenic | -0.775 | Destabilizing | 1.0 | D | 0.758 | deleterious | None | None | None | None | N |
| A/D | 0.9644 | likely_pathogenic | 0.9529 | pathogenic | -0.811 | Destabilizing | 0.988 | D | 0.729 | prob.delet. | N | 0.477749687 | None | None | N |
| A/E | 0.929 | likely_pathogenic | 0.9061 | pathogenic | -0.914 | Destabilizing | 0.991 | D | 0.692 | prob.neutral | None | None | None | None | N |
| A/F | 0.8175 | likely_pathogenic | 0.7539 | pathogenic | -1.006 | Destabilizing | 0.995 | D | 0.753 | deleterious | None | None | None | None | N |
| A/G | 0.5803 | likely_pathogenic | 0.4994 | ambiguous | -0.85 | Destabilizing | 0.919 | D | 0.567 | neutral | N | 0.470901073 | None | None | N |
| A/H | 0.91 | likely_pathogenic | 0.8841 | pathogenic | -0.857 | Destabilizing | 1.0 | D | 0.751 | deleterious | None | None | None | None | N |
| A/I | 0.7228 | likely_pathogenic | 0.6032 | pathogenic | -0.473 | Destabilizing | 0.995 | D | 0.747 | deleterious | None | None | None | None | N |
| A/K | 0.968 | likely_pathogenic | 0.9608 | pathogenic | -1.044 | Destabilizing | 0.991 | D | 0.705 | prob.neutral | None | None | None | None | N |
| A/L | 0.5324 | ambiguous | 0.4512 | ambiguous | -0.473 | Destabilizing | 0.968 | D | 0.666 | neutral | None | None | None | None | N |
| A/M | 0.6251 | likely_pathogenic | 0.501 | ambiguous | -0.425 | Destabilizing | 1.0 | D | 0.757 | deleterious | None | None | None | None | N |
| A/N | 0.7877 | likely_pathogenic | 0.7313 | pathogenic | -0.696 | Destabilizing | 0.991 | D | 0.727 | prob.delet. | None | None | None | None | N |
| A/P | 0.9711 | likely_pathogenic | 0.9506 | pathogenic | -0.51 | Destabilizing | 0.994 | D | 0.749 | deleterious | N | 0.521463179 | None | None | N |
| A/Q | 0.8162 | likely_pathogenic | 0.7691 | pathogenic | -0.946 | Destabilizing | 0.991 | D | 0.762 | deleterious | None | None | None | None | N |
| A/R | 0.919 | likely_pathogenic | 0.9087 | pathogenic | -0.545 | Destabilizing | 0.991 | D | 0.757 | deleterious | None | None | None | None | N |
| A/S | 0.2648 | likely_benign | 0.226 | benign | -0.958 | Destabilizing | 0.414 | N | 0.332 | neutral | N | 0.456123621 | None | None | N |
| A/T | 0.4194 | ambiguous | 0.3063 | benign | -0.98 | Destabilizing | 0.919 | D | 0.635 | neutral | N | 0.389514627 | None | None | N |
| A/V | 0.4832 | ambiguous | 0.359 | ambiguous | -0.51 | Destabilizing | 0.958 | D | 0.651 | neutral | N | 0.389975987 | None | None | N |
| A/W | 0.9715 | likely_pathogenic | 0.9572 | pathogenic | -1.215 | Destabilizing | 1.0 | D | 0.793 | deleterious | None | None | None | None | N |
| A/Y | 0.8963 | likely_pathogenic | 0.8601 | pathogenic | -0.867 | Destabilizing | 1.0 | D | 0.751 | 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.