Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28940 | 87043;87044;87045 | chr2:178559314;178559313;178559312 | chr2:179424041;179424040;179424039 |
| N2AB | 27299 | 82120;82121;82122 | chr2:178559314;178559313;178559312 | chr2:179424041;179424040;179424039 |
| N2A | 26372 | 79339;79340;79341 | chr2:178559314;178559313;178559312 | chr2:179424041;179424040;179424039 |
| N2B | 19875 | 59848;59849;59850 | chr2:178559314;178559313;178559312 | chr2:179424041;179424040;179424039 |
| Novex-1 | 20000 | 60223;60224;60225 | chr2:178559314;178559313;178559312 | chr2:179424041;179424040;179424039 |
| Novex-2 | 20067 | 60424;60425;60426 | chr2:178559314;178559313;178559312 | chr2:179424041;179424040;179424039 |
| 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 | rs748476449  |
-0.782 | 0.997 | N | 0.482 | 0.285 | 0.144782658237 | gnomAD-2.1.1 | 1.14E-05 | None | None | None | None | N | None | 1.25786E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| T/A | rs748476449 |
-0.782 | 0.997 | N | 0.482 | 0.285 | 0.144782658237 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 4.82E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| T/A | rs748476449 |
-0.782 | 0.997 | N | 0.482 | 0.285 | 0.144782658237 | gnomAD-4.0.0 | 5.67686E-06 | None | None | None | None | N | None | 1.22386E-04 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| T/I | None | None | 0.999 | N | 0.612 | 0.361 | 0.340273420219 | gnomAD-4.0.0 | 1.6663E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.97869E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.1372 | likely_benign | 0.1343 | benign | -0.738 | Destabilizing | 0.997 | D | 0.482 | neutral | N | 0.389029051 | None | None | N |
| T/C | 0.4826 | ambiguous | 0.5056 | ambiguous | -0.567 | Destabilizing | 1.0 | D | 0.651 | prob.neutral | None | None | None | None | N |
| T/D | 0.8789 | likely_pathogenic | 0.9104 | pathogenic | -0.189 | Destabilizing | 0.999 | D | 0.633 | neutral | None | None | None | None | N |
| T/E | 0.7684 | likely_pathogenic | 0.8203 | pathogenic | -0.209 | Destabilizing | 0.999 | D | 0.635 | neutral | None | None | None | None | N |
| T/F | 0.64 | likely_pathogenic | 0.7074 | pathogenic | -0.832 | Destabilizing | 0.999 | D | 0.681 | prob.neutral | None | None | None | None | N |
| T/G | 0.4433 | ambiguous | 0.4775 | ambiguous | -0.969 | Destabilizing | 0.999 | D | 0.591 | neutral | None | None | None | None | N |
| T/H | 0.677 | likely_pathogenic | 0.749 | pathogenic | -1.236 | Destabilizing | 1.0 | D | 0.697 | prob.delet. | None | None | None | None | N |
| T/I | 0.5078 | ambiguous | 0.5844 | pathogenic | -0.223 | Destabilizing | 0.999 | D | 0.612 | neutral | N | 0.452309738 | None | None | N |
| T/K | 0.5536 | ambiguous | 0.6658 | pathogenic | -0.783 | Destabilizing | 0.999 | D | 0.642 | neutral | N | 0.413234062 | None | None | N |
| T/L | 0.2128 | likely_benign | 0.2612 | benign | -0.223 | Destabilizing | 0.998 | D | 0.643 | neutral | None | None | None | None | N |
| T/M | 0.1124 | likely_benign | 0.1308 | benign | 0.003 | Stabilizing | 1.0 | D | 0.617 | neutral | None | None | None | None | N |
| T/N | 0.4124 | ambiguous | 0.4866 | ambiguous | -0.667 | Destabilizing | 0.999 | D | 0.641 | neutral | None | None | None | None | N |
| T/P | 0.6617 | likely_pathogenic | 0.756 | pathogenic | -0.363 | Destabilizing | 0.999 | D | 0.574 | neutral | N | 0.437761573 | None | None | N |
| T/Q | 0.4922 | ambiguous | 0.5758 | pathogenic | -0.873 | Destabilizing | 0.999 | D | 0.629 | neutral | None | None | None | None | N |
| T/R | 0.425 | ambiguous | 0.5255 | ambiguous | -0.504 | Destabilizing | 0.999 | D | 0.583 | neutral | N | 0.43441741 | None | None | N |
| T/S | 0.1708 | likely_benign | 0.1779 | benign | -0.936 | Destabilizing | 0.997 | D | 0.553 | neutral | N | 0.363343959 | None | None | N |
| T/V | 0.305 | likely_benign | 0.3479 | ambiguous | -0.363 | Destabilizing | 0.998 | D | 0.613 | neutral | None | None | None | None | N |
| T/W | 0.8786 | likely_pathogenic | 0.9112 | pathogenic | -0.748 | Destabilizing | 1.0 | D | 0.645 | neutral | None | None | None | None | N |
| T/Y | 0.7392 | likely_pathogenic | 0.8073 | pathogenic | -0.532 | Destabilizing | 1.0 | D | 0.695 | prob.delet. | 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.