Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25748 | 77467;77468;77469 | chr2:178568890;178568889;178568888 | chr2:179433617;179433616;179433615 |
| N2AB | 24107 | 72544;72545;72546 | chr2:178568890;178568889;178568888 | chr2:179433617;179433616;179433615 |
| N2A | 23180 | 69763;69764;69765 | chr2:178568890;178568889;178568888 | chr2:179433617;179433616;179433615 |
| N2B | 16683 | 50272;50273;50274 | chr2:178568890;178568889;178568888 | chr2:179433617;179433616;179433615 |
| Novex-1 | 16808 | 50647;50648;50649 | chr2:178568890;178568889;178568888 | chr2:179433617;179433616;179433615 |
| Novex-2 | 16875 | 50848;50849;50850 | chr2:178568890;178568889;178568888 | chr2:179433617;179433616;179433615 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| C/R | rs1162453553  |
None | 0.992 | N | 0.811 | 0.45 | 0.623733534801 | 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 |
| C/R | rs1162453553 |
None | 0.992 | N | 0.811 | 0.45 | 0.623733534801 | gnomAD-4.0.0 | 2.56433E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.39423E-06 | 1.34055E-05 | 0 |
| C/Y | rs772628162 |
-0.988 | 0.998 | N | 0.782 | 0.283 | 0.691146523942 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.88E-06 | 0 |
| C/Y | rs772628162 |
-0.988 | 0.998 | N | 0.782 | 0.283 | 0.691146523942 | gnomAD-4.0.0 | 3.42228E-06 | None | None | None | None | N | None | 2.99043E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 2.69883E-06 | 1.15972E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| C/A | 0.4138 | ambiguous | 0.3869 | ambiguous | -1.351 | Destabilizing | 0.021 | N | 0.259 | neutral | None | None | None | None | N |
| C/D | 0.959 | likely_pathogenic | 0.9511 | pathogenic | 0.07 | Stabilizing | 0.956 | D | 0.791 | deleterious | None | None | None | None | N |
| C/E | 0.9653 | likely_pathogenic | 0.961 | pathogenic | 0.121 | Stabilizing | 0.97 | D | 0.792 | deleterious | None | None | None | None | N |
| C/F | 0.4364 | ambiguous | 0.3992 | ambiguous | -0.891 | Destabilizing | 0.992 | D | 0.781 | deleterious | N | 0.477592847 | None | None | N |
| C/G | 0.3275 | likely_benign | 0.3022 | benign | -1.605 | Destabilizing | 0.652 | D | 0.697 | prob.neutral | N | 0.471733952 | None | None | N |
| C/H | 0.847 | likely_pathogenic | 0.8333 | pathogenic | -1.524 | Destabilizing | 0.999 | D | 0.785 | deleterious | None | None | None | None | N |
| C/I | 0.5342 | ambiguous | 0.4937 | ambiguous | -0.728 | Destabilizing | 0.989 | D | 0.657 | neutral | None | None | None | None | N |
| C/K | 0.9516 | likely_pathogenic | 0.9414 | pathogenic | -0.6 | Destabilizing | 0.989 | D | 0.783 | deleterious | None | None | None | None | N |
| C/L | 0.6867 | likely_pathogenic | 0.6501 | pathogenic | -0.728 | Destabilizing | 0.925 | D | 0.53 | neutral | None | None | None | None | N |
| C/M | 0.7302 | likely_pathogenic | 0.7178 | pathogenic | -0.027 | Destabilizing | 1.0 | D | 0.729 | prob.delet. | None | None | None | None | N |
| C/N | 0.8414 | likely_pathogenic | 0.8229 | pathogenic | -0.471 | Destabilizing | 0.979 | D | 0.813 | deleterious | None | None | None | None | N |
| C/P | 0.9796 | likely_pathogenic | 0.9741 | pathogenic | -0.91 | Destabilizing | 0.956 | D | 0.807 | deleterious | None | None | None | None | N |
| C/Q | 0.8903 | likely_pathogenic | 0.8808 | pathogenic | -0.468 | Destabilizing | 0.985 | D | 0.803 | deleterious | None | None | None | None | N |
| C/R | 0.8263 | likely_pathogenic | 0.8033 | pathogenic | -0.344 | Destabilizing | 0.992 | D | 0.811 | deleterious | N | 0.489874206 | None | None | N |
| C/S | 0.4924 | ambiguous | 0.4828 | ambiguous | -1.011 | Destabilizing | 0.722 | D | 0.531 | neutral | N | 0.467757479 | None | None | N |
| C/T | 0.5574 | ambiguous | 0.5373 | ambiguous | -0.792 | Destabilizing | 0.868 | D | 0.59 | neutral | None | None | None | None | N |
| C/V | 0.3392 | likely_benign | 0.3163 | benign | -0.91 | Destabilizing | 0.822 | D | 0.531 | neutral | None | None | None | None | N |
| C/W | 0.8503 | likely_pathogenic | 0.8382 | pathogenic | -0.832 | Destabilizing | 0.999 | D | 0.763 | deleterious | N | 0.510766845 | None | None | N |
| C/Y | 0.5987 | likely_pathogenic | 0.5705 | pathogenic | -0.802 | Destabilizing | 0.998 | D | 0.782 | deleterious | N | 0.465631112 | 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.