Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15898 | 47917;47918;47919 | chr2:178617393;178617392;178617391 | chr2:179482120;179482119;179482118 |
| N2AB | 14257 | 42994;42995;42996 | chr2:178617393;178617392;178617391 | chr2:179482120;179482119;179482118 |
| N2A | 13330 | 40213;40214;40215 | chr2:178617393;178617392;178617391 | chr2:179482120;179482119;179482118 |
| N2B | 6833 | 20722;20723;20724 | chr2:178617393;178617392;178617391 | chr2:179482120;179482119;179482118 |
| Novex-1 | 6958 | 21097;21098;21099 | chr2:178617393;178617392;178617391 | chr2:179482120;179482119;179482118 |
| Novex-2 | 7025 | 21298;21299;21300 | chr2:178617393;178617392;178617391 | chr2:179482120;179482119;179482118 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/G | None | None | 0.868 | D | 0.733 | 0.324 | 0.351830644314 | gnomAD-4.0.0 | 3.30856E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.86541E-06 | 0 | 0 |
| R/L | None | None | 0.768 | N | 0.715 | 0.264 | 0.405560941015 | gnomAD-4.0.0 | 6.95707E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.06793E-07 | 0 | 0 |
| R/P | rs376278449  |
-1.556 | 0.979 | D | 0.767 | 0.364 | 0.42828666871 | gnomAD-2.1.1 | 9.19E-06 | None | None | None | None | N | None | 0 | 6.91E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| R/P | rs376278449 |
-1.556 | 0.979 | D | 0.767 | 0.364 | 0.42828666871 | gnomAD-3.1.2 | 6.59E-06 | None | None | None | None | N | None | 0 | 6.57E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/P | rs376278449 |
-1.556 | 0.979 | D | 0.767 | 0.364 | 0.42828666871 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 1.4E-03 | None | None | 0 | 0 | None | None | None | 0 | None |
| R/P | rs376278449 |
-1.556 | 0.979 | D | 0.767 | 0.364 | 0.42828666871 | gnomAD-4.0.0 | 1.25838E-06 | None | None | None | None | N | None | 0 | 3.6547E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/Q | rs376278449 |
-1.72 | 0.981 | D | 0.613 | 0.243 | None | gnomAD-2.1.1 | 5.22E-05 | None | None | None | None | N | None | 0 | 2.01478E-04 | None | 0 | 5.71E-05 | None | 0 | None | 0 | 3.48E-05 | 3.07031E-04 |
| R/Q | rs376278449 |
-1.72 | 0.981 | D | 0.613 | 0.243 | None | gnomAD-3.1.2 | 6.59E-05 | None | None | None | None | N | None | 4.83E-05 | 4.59982E-04 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/Q | rs376278449 |
-1.72 | 0.981 | D | 0.613 | 0.243 | None | gnomAD-4.0.0 | 7.36207E-05 | None | None | None | None | N | None | 2.71444E-05 | 2.55923E-04 | None | 0 | 2.2605E-05 | None | 0 | 3.32226E-04 | 7.94417E-05 | 0 | 8.13087E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.6368 | likely_pathogenic | 0.7009 | pathogenic | -2.099 | Highly Destabilizing | 0.775 | D | 0.652 | neutral | None | None | None | None | N |
| R/C | 0.1961 | likely_benign | 0.2357 | benign | -2.101 | Highly Destabilizing | 0.996 | D | 0.779 | deleterious | None | None | None | None | N |
| R/D | 0.9319 | likely_pathogenic | 0.952 | pathogenic | -1.691 | Destabilizing | 0.923 | D | 0.738 | prob.delet. | None | None | None | None | N |
| R/E | 0.6212 | likely_pathogenic | 0.6867 | pathogenic | -1.433 | Destabilizing | 0.633 | D | 0.585 | neutral | None | None | None | None | N |
| R/F | 0.6197 | likely_pathogenic | 0.6675 | pathogenic | -1.036 | Destabilizing | 0.858 | D | 0.781 | deleterious | None | None | None | None | N |
| R/G | 0.5598 | ambiguous | 0.6588 | pathogenic | -2.485 | Highly Destabilizing | 0.868 | D | 0.733 | prob.delet. | D | 0.544285071 | None | None | N |
| R/H | 0.1874 | likely_benign | 0.1935 | benign | -1.828 | Destabilizing | 0.923 | D | 0.596 | neutral | None | None | None | None | N |
| R/I | 0.3356 | likely_benign | 0.3966 | ambiguous | -0.953 | Destabilizing | 0.923 | D | 0.781 | deleterious | None | None | None | None | N |
| R/K | 0.1215 | likely_benign | 0.1417 | benign | -1.392 | Destabilizing | 0.044 | N | 0.331 | neutral | None | None | None | None | N |
| R/L | 0.3612 | ambiguous | 0.4028 | ambiguous | -0.953 | Destabilizing | 0.768 | D | 0.715 | prob.delet. | N | 0.489747338 | None | None | N |
| R/M | 0.3202 | likely_benign | 0.3751 | ambiguous | -1.405 | Destabilizing | 0.996 | D | 0.713 | prob.delet. | None | None | None | None | N |
| R/N | 0.8131 | likely_pathogenic | 0.8571 | pathogenic | -2.021 | Highly Destabilizing | 0.923 | D | 0.585 | neutral | None | None | None | None | N |
| R/P | 0.9898 | likely_pathogenic | 0.9891 | pathogenic | -1.326 | Destabilizing | 0.979 | D | 0.767 | deleterious | D | 0.670657134 | None | None | N |
| R/Q | 0.156 | likely_benign | 0.1737 | benign | -1.744 | Destabilizing | 0.981 | D | 0.613 | neutral | D | 0.531184795 | None | None | N |
| R/S | 0.7291 | likely_pathogenic | 0.7898 | pathogenic | -2.779 | Highly Destabilizing | 0.775 | D | 0.658 | neutral | None | None | None | None | N |
| R/T | 0.4825 | ambiguous | 0.568 | pathogenic | -2.285 | Highly Destabilizing | 0.875 | D | 0.677 | prob.neutral | None | None | None | None | N |
| R/V | 0.4176 | ambiguous | 0.4955 | ambiguous | -1.326 | Destabilizing | 0.923 | D | 0.756 | deleterious | None | None | None | None | N |
| R/W | 0.3173 | likely_benign | 0.3208 | benign | -0.55 | Destabilizing | 0.989 | D | 0.776 | deleterious | None | None | None | None | N |
| R/Y | 0.4041 | ambiguous | 0.4374 | ambiguous | -0.503 | Destabilizing | 0.024 | N | 0.583 | 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.