Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16651 | 50176;50177;50178 | chr2:178612574;178612573;178612572 | chr2:179477301;179477300;179477299 |
| N2AB | 15010 | 45253;45254;45255 | chr2:178612574;178612573;178612572 | chr2:179477301;179477300;179477299 |
| N2A | 14083 | 42472;42473;42474 | chr2:178612574;178612573;178612572 | chr2:179477301;179477300;179477299 |
| N2B | 7586 | 22981;22982;22983 | chr2:178612574;178612573;178612572 | chr2:179477301;179477300;179477299 |
| Novex-1 | 7711 | 23356;23357;23358 | chr2:178612574;178612573;178612572 | chr2:179477301;179477300;179477299 |
| Novex-2 | 7778 | 23557;23558;23559 | chr2:178612574;178612573;178612572 | chr2:179477301;179477300;179477299 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/H | None | None | 1.0 | D | 0.861 | 0.4 | 0.522129480193 | gnomAD-4.0.0 | 6.89576E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.20514E-05 | 0 |
| P/S | rs537759268  |
None | 1.0 | N | 0.816 | 0.384 | 0.283761946502 | gnomAD-3.1.2 | 6.65E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| P/S | rs537759268 |
None | 1.0 | N | 0.816 | 0.384 | 0.283761946502 | gnomAD-4.0.0 | 2.50083E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.40097E-06 | 0 | 0 |
| P/T | rs537759268 |
-0.503 | 1.0 | N | 0.805 | 0.313 | 0.367042808489 | gnomAD-2.1.1 | 4.36E-06 | None | None | None | None | I | None | 0 | 3.19E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| P/T | rs537759268 |
-0.503 | 1.0 | N | 0.805 | 0.313 | 0.367042808489 | 1000 genomes | 1.99681E-04 | None | None | None | None | I | None | 0 | 1.4E-03 | None | None | 0 | 0 | None | None | None | 0 | None |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.1715 | likely_benign | 0.2043 | benign | -0.641 | Destabilizing | 0.999 | D | 0.789 | deleterious | N | 0.448169664 | None | None | I |
| P/C | 0.7858 | likely_pathogenic | 0.8122 | pathogenic | -0.705 | Destabilizing | 1.0 | D | 0.857 | deleterious | None | None | None | None | I |
| P/D | 0.9365 | likely_pathogenic | 0.9634 | pathogenic | -0.17 | Destabilizing | 1.0 | D | 0.813 | deleterious | None | None | None | None | I |
| P/E | 0.7029 | likely_pathogenic | 0.7833 | pathogenic | -0.279 | Destabilizing | 1.0 | D | 0.813 | deleterious | None | None | None | None | I |
| P/F | 0.8315 | likely_pathogenic | 0.888 | pathogenic | -0.924 | Destabilizing | 1.0 | D | 0.873 | deleterious | None | None | None | None | I |
| P/G | 0.7698 | likely_pathogenic | 0.8267 | pathogenic | -0.774 | Destabilizing | 1.0 | D | 0.873 | deleterious | None | None | None | None | I |
| P/H | 0.5381 | ambiguous | 0.6527 | pathogenic | -0.333 | Destabilizing | 1.0 | D | 0.861 | deleterious | D | 0.570609198 | None | None | I |
| P/I | 0.509 | ambiguous | 0.523 | ambiguous | -0.439 | Destabilizing | 1.0 | D | 0.853 | deleterious | None | None | None | None | I |
| P/K | 0.5498 | ambiguous | 0.6206 | pathogenic | -0.293 | Destabilizing | 1.0 | D | 0.81 | deleterious | None | None | None | None | I |
| P/L | 0.2702 | likely_benign | 0.3135 | benign | -0.439 | Destabilizing | 1.0 | D | 0.839 | deleterious | N | 0.485329663 | None | None | I |
| P/M | 0.6351 | likely_pathogenic | 0.6588 | pathogenic | -0.307 | Destabilizing | 1.0 | D | 0.857 | deleterious | None | None | None | None | I |
| P/N | 0.8266 | likely_pathogenic | 0.8734 | pathogenic | -0.074 | Destabilizing | 1.0 | D | 0.872 | deleterious | None | None | None | None | I |
| P/Q | 0.3857 | ambiguous | 0.4375 | ambiguous | -0.358 | Destabilizing | 1.0 | D | 0.819 | deleterious | None | None | None | None | I |
| P/R | 0.3653 | ambiguous | 0.4613 | ambiguous | 0.196 | Stabilizing | 1.0 | D | 0.867 | deleterious | N | 0.467182752 | None | None | I |
| P/S | 0.3866 | ambiguous | 0.4781 | ambiguous | -0.522 | Destabilizing | 1.0 | D | 0.816 | deleterious | N | 0.513811048 | None | None | I |
| P/T | 0.325 | likely_benign | 0.3565 | ambiguous | -0.529 | Destabilizing | 1.0 | D | 0.805 | deleterious | N | 0.475025427 | None | None | I |
| P/V | 0.3657 | ambiguous | 0.3672 | ambiguous | -0.472 | Destabilizing | 1.0 | D | 0.862 | deleterious | None | None | None | None | I |
| P/W | 0.9416 | likely_pathogenic | 0.9629 | pathogenic | -0.952 | Destabilizing | 1.0 | D | 0.831 | deleterious | None | None | None | None | I |
| P/Y | 0.8218 | likely_pathogenic | 0.8948 | pathogenic | -0.625 | Destabilizing | 1.0 | D | 0.868 | deleterious | None | None | None | None | I |
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.