Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1714 | 5365;5366;5367 | chr2:178776724;178776723;178776722 | chr2:179641451;179641450;179641449 |
| N2AB | 1714 | 5365;5366;5367 | chr2:178776724;178776723;178776722 | chr2:179641451;179641450;179641449 |
| N2A | 1714 | 5365;5366;5367 | chr2:178776724;178776723;178776722 | chr2:179641451;179641450;179641449 |
| N2B | 1668 | 5227;5228;5229 | chr2:178776724;178776723;178776722 | chr2:179641451;179641450;179641449 |
| Novex-1 | 1668 | 5227;5228;5229 | chr2:178776724;178776723;178776722 | chr2:179641451;179641450;179641449 |
| Novex-2 | 1668 | 5227;5228;5229 | chr2:178776724;178776723;178776722 | chr2:179641451;179641450;179641449 |
| Novex-3 | 1714 | 5365;5366;5367 | chr2:178776724;178776723;178776722 | chr2:179641451;179641450;179641449 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/F | rs2092264988  |
None | 0.994 | D | 0.617 | 0.353 | 0.628758500363 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| L/F | rs2092264988 |
None | 0.994 | D | 0.617 | 0.353 | 0.628758500363 | gnomAD-4.0.0 | 2.56119E-06 | None | None | None | None | I | None | 1.69096E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 2.39167E-06 | 0 | 0 |
| L/H | rs750997358 |
-1.699 | 1.0 | D | 0.634 | 0.604 | 0.900287583318 | gnomAD-2.1.1 | 3.99E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.84E-06 | 0 |
| L/H | rs750997358 |
-1.699 | 1.0 | D | 0.634 | 0.604 | 0.900287583318 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| L/H | rs750997358 |
-1.699 | 1.0 | D | 0.634 | 0.604 | 0.900287583318 | gnomAD-4.0.0 | 6.57039E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.46977E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.6243 | likely_pathogenic | 0.6544 | pathogenic | -1.994 | Destabilizing | 0.983 | D | 0.523 | neutral | None | None | None | None | I |
| L/C | 0.7797 | likely_pathogenic | 0.7939 | pathogenic | -1.145 | Destabilizing | 1.0 | D | 0.576 | neutral | None | None | None | None | I |
| L/D | 0.9694 | likely_pathogenic | 0.9766 | pathogenic | -1.7 | Destabilizing | 0.999 | D | 0.684 | prob.neutral | None | None | None | None | I |
| L/E | 0.787 | likely_pathogenic | 0.8098 | pathogenic | -1.607 | Destabilizing | 0.999 | D | 0.684 | prob.neutral | None | None | None | None | I |
| L/F | 0.4131 | ambiguous | 0.4431 | ambiguous | -1.176 | Destabilizing | 0.994 | D | 0.617 | neutral | D | 0.571715188 | None | None | I |
| L/G | 0.8641 | likely_pathogenic | 0.8843 | pathogenic | -2.413 | Highly Destabilizing | 0.998 | D | 0.679 | prob.neutral | None | None | None | None | I |
| L/H | 0.6905 | likely_pathogenic | 0.7356 | pathogenic | -1.703 | Destabilizing | 1.0 | D | 0.634 | neutral | D | 0.593101169 | None | None | I |
| L/I | 0.1707 | likely_benign | 0.1788 | benign | -0.857 | Destabilizing | 0.956 | D | 0.466 | neutral | N | 0.492885905 | None | None | I |
| L/K | 0.7183 | likely_pathogenic | 0.7602 | pathogenic | -1.547 | Destabilizing | 0.998 | D | 0.633 | neutral | None | None | None | None | I |
| L/M | 0.1403 | likely_benign | 0.142 | benign | -0.636 | Destabilizing | 0.693 | D | 0.343 | neutral | None | None | None | None | I |
| L/N | 0.8011 | likely_pathogenic | 0.8385 | pathogenic | -1.496 | Destabilizing | 0.999 | D | 0.681 | prob.neutral | None | None | None | None | I |
| L/P | 0.943 | likely_pathogenic | 0.9621 | pathogenic | -1.208 | Destabilizing | 0.999 | D | 0.682 | prob.neutral | D | 0.685377027 | None | None | I |
| L/Q | 0.4096 | ambiguous | 0.4445 | ambiguous | -1.553 | Destabilizing | 0.998 | D | 0.637 | neutral | None | None | None | None | I |
| L/R | 0.6511 | likely_pathogenic | 0.7027 | pathogenic | -1.033 | Destabilizing | 0.997 | D | 0.64 | neutral | D | 0.535290571 | None | None | I |
| L/S | 0.7245 | likely_pathogenic | 0.7636 | pathogenic | -2.149 | Highly Destabilizing | 0.998 | D | 0.631 | neutral | None | None | None | None | I |
| L/T | 0.5302 | ambiguous | 0.5731 | pathogenic | -1.938 | Destabilizing | 0.998 | D | 0.648 | neutral | None | None | None | None | I |
| L/V | 0.1639 | likely_benign | 0.1692 | benign | -1.208 | Destabilizing | 0.9 | D | 0.478 | neutral | N | 0.414765681 | None | None | I |
| L/W | 0.7103 | likely_pathogenic | 0.7677 | pathogenic | -1.405 | Destabilizing | 1.0 | D | 0.599 | neutral | None | None | None | None | I |
| L/Y | 0.7706 | likely_pathogenic | 0.8081 | pathogenic | -1.16 | Destabilizing | 0.999 | D | 0.629 | neutral | 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.