Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26771 | 80536;80537;80538 | chr2:178565821;178565820;178565819 | chr2:179430548;179430547;179430546 |
| N2AB | 25130 | 75613;75614;75615 | chr2:178565821;178565820;178565819 | chr2:179430548;179430547;179430546 |
| N2A | 24203 | 72832;72833;72834 | chr2:178565821;178565820;178565819 | chr2:179430548;179430547;179430546 |
| N2B | 17706 | 53341;53342;53343 | chr2:178565821;178565820;178565819 | chr2:179430548;179430547;179430546 |
| Novex-1 | 17831 | 53716;53717;53718 | chr2:178565821;178565820;178565819 | chr2:179430548;179430547;179430546 |
| Novex-2 | 17898 | 53917;53918;53919 | chr2:178565821;178565820;178565819 | chr2:179430548;179430547;179430546 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | None | None | 0.986 | N | 0.66 | 0.49 | 0.309839678437 | 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 |
| T/I | rs567184856  |
0.181 | 1.0 | N | 0.903 | 0.466 | 0.389750110748 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| T/I | rs567184856 |
0.181 | 1.0 | N | 0.903 | 0.466 | 0.389750110748 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.07383E-04 | 0 |
| T/I | rs567184856 |
0.181 | 1.0 | N | 0.903 | 0.466 | 0.389750110748 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 1E-03 | None |
| T/I | rs567184856 |
0.181 | 1.0 | N | 0.903 | 0.466 | 0.389750110748 | gnomAD-4.0.0 | 2.56247E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.68053E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.3808 | ambiguous | 0.3857 | ambiguous | -0.914 | Destabilizing | 0.986 | D | 0.66 | prob.neutral | N | 0.476667795 | None | None | N |
| T/C | 0.8248 | likely_pathogenic | 0.825 | pathogenic | -0.439 | Destabilizing | 1.0 | D | 0.846 | deleterious | None | None | None | None | N |
| T/D | 0.9469 | likely_pathogenic | 0.9431 | pathogenic | -0.771 | Destabilizing | 0.999 | D | 0.883 | deleterious | None | None | None | None | N |
| T/E | 0.9392 | likely_pathogenic | 0.9357 | pathogenic | -0.607 | Destabilizing | 1.0 | D | 0.881 | deleterious | None | None | None | None | N |
| T/F | 0.8716 | likely_pathogenic | 0.8722 | pathogenic | -0.483 | Destabilizing | 1.0 | D | 0.905 | deleterious | None | None | None | None | N |
| T/G | 0.7182 | likely_pathogenic | 0.7187 | pathogenic | -1.318 | Destabilizing | 1.0 | D | 0.836 | deleterious | None | None | None | None | N |
| T/H | 0.9207 | likely_pathogenic | 0.9164 | pathogenic | -1.4 | Destabilizing | 1.0 | D | 0.878 | deleterious | None | None | None | None | N |
| T/I | 0.5784 | likely_pathogenic | 0.5508 | ambiguous | 0.135 | Stabilizing | 1.0 | D | 0.903 | deleterious | N | 0.463563516 | None | None | N |
| T/K | 0.9334 | likely_pathogenic | 0.9304 | pathogenic | -0.473 | Destabilizing | 1.0 | D | 0.881 | deleterious | None | None | None | None | N |
| T/L | 0.2719 | likely_benign | 0.294 | benign | 0.135 | Stabilizing | 0.999 | D | 0.791 | deleterious | None | None | None | None | N |
| T/M | 0.1746 | likely_benign | 0.1813 | benign | 0.111 | Stabilizing | 1.0 | D | 0.834 | deleterious | None | None | None | None | N |
| T/N | 0.6025 | likely_pathogenic | 0.5878 | pathogenic | -0.913 | Destabilizing | 0.999 | D | 0.805 | deleterious | N | 0.491595726 | None | None | N |
| T/P | 0.8415 | likely_pathogenic | 0.7979 | pathogenic | -0.182 | Destabilizing | 0.999 | D | 0.887 | deleterious | N | 0.507296229 | None | None | N |
| T/Q | 0.9016 | likely_pathogenic | 0.9003 | pathogenic | -0.731 | Destabilizing | 1.0 | D | 0.883 | deleterious | None | None | None | None | N |
| T/R | 0.93 | likely_pathogenic | 0.9257 | pathogenic | -0.633 | Destabilizing | 1.0 | D | 0.891 | deleterious | None | None | None | None | N |
| T/S | 0.398 | ambiguous | 0.3889 | ambiguous | -1.19 | Destabilizing | 0.986 | D | 0.66 | prob.neutral | N | 0.506970942 | None | None | N |
| T/V | 0.4578 | ambiguous | 0.4531 | ambiguous | -0.182 | Destabilizing | 0.999 | D | 0.723 | deleterious | None | None | None | None | N |
| T/W | 0.9773 | likely_pathogenic | 0.9756 | pathogenic | -0.61 | Destabilizing | 1.0 | D | 0.857 | deleterious | None | None | None | None | N |
| T/Y | 0.9206 | likely_pathogenic | 0.9185 | pathogenic | -0.262 | Destabilizing | 1.0 | D | 0.912 | 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.