Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1770 | 5533;5534;5535 | chr2:178776556;178776555;178776554 | chr2:179641283;179641282;179641281 |
| N2AB | 1770 | 5533;5534;5535 | chr2:178776556;178776555;178776554 | chr2:179641283;179641282;179641281 |
| N2A | 1770 | 5533;5534;5535 | chr2:178776556;178776555;178776554 | chr2:179641283;179641282;179641281 |
| N2B | 1724 | 5395;5396;5397 | chr2:178776556;178776555;178776554 | chr2:179641283;179641282;179641281 |
| Novex-1 | 1724 | 5395;5396;5397 | chr2:178776556;178776555;178776554 | chr2:179641283;179641282;179641281 |
| Novex-2 | 1724 | 5395;5396;5397 | chr2:178776556;178776555;178776554 | chr2:179641283;179641282;179641281 |
| Novex-3 | 1770 | 5533;5534;5535 | chr2:178776556;178776555;178776554 | chr2:179641283;179641282;179641281 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/G | rs780733773  |
-0.228 | 1.0 | N | 0.649 | 0.568 | 0.647459595057 | gnomAD-2.1.1 | 2.8E-05 | None | None | None | None | I | None | 0 | 8.68E-05 | None | 0 | 0 | None | 0 | None | 0 | 2.65E-05 | 1.63452E-04 |
| R/G | rs780733773 |
-0.228 | 1.0 | N | 0.649 | 0.568 | 0.647459595057 | gnomAD-4.0.0 | 1.16412E-05 | None | None | None | None | I | None | 0 | 8.94534E-05 | None | 3.82643E-05 | 0 | None | 0 | 0 | 1.07917E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.9393 | likely_pathogenic | 0.9208 | pathogenic | -0.155 | Destabilizing | 0.999 | D | 0.645 | neutral | None | None | None | None | I |
| R/C | 0.8768 | likely_pathogenic | 0.8658 | pathogenic | -0.257 | Destabilizing | 1.0 | D | 0.8 | deleterious | None | None | None | None | I |
| R/D | 0.978 | likely_pathogenic | 0.9717 | pathogenic | -0.024 | Destabilizing | 1.0 | D | 0.749 | deleterious | None | None | None | None | I |
| R/E | 0.9135 | likely_pathogenic | 0.8866 | pathogenic | 0.047 | Stabilizing | 0.999 | D | 0.709 | prob.delet. | None | None | None | None | I |
| R/F | 0.9866 | likely_pathogenic | 0.9807 | pathogenic | -0.395 | Destabilizing | 1.0 | D | 0.769 | deleterious | None | None | None | None | I |
| R/G | 0.8704 | likely_pathogenic | 0.8032 | pathogenic | -0.353 | Destabilizing | 1.0 | D | 0.649 | neutral | N | 0.505227739 | None | None | I |
| R/H | 0.6122 | likely_pathogenic | 0.5679 | pathogenic | -0.922 | Destabilizing | 1.0 | D | 0.815 | deleterious | None | None | None | None | I |
| R/I | 0.9533 | likely_pathogenic | 0.9384 | pathogenic | 0.333 | Stabilizing | 1.0 | D | 0.776 | deleterious | D | 0.563936144 | None | None | I |
| R/K | 0.4511 | ambiguous | 0.4194 | ambiguous | -0.16 | Destabilizing | 0.997 | D | 0.561 | neutral | N | 0.512950813 | None | None | I |
| R/L | 0.9017 | likely_pathogenic | 0.8703 | pathogenic | 0.333 | Stabilizing | 1.0 | D | 0.649 | neutral | None | None | None | None | I |
| R/M | 0.9604 | likely_pathogenic | 0.9437 | pathogenic | -0.06 | Destabilizing | 1.0 | D | 0.77 | deleterious | None | None | None | None | I |
| R/N | 0.9685 | likely_pathogenic | 0.963 | pathogenic | 0.083 | Stabilizing | 1.0 | D | 0.78 | deleterious | None | None | None | None | I |
| R/P | 0.9534 | likely_pathogenic | 0.9423 | pathogenic | 0.191 | Stabilizing | 1.0 | D | 0.744 | deleterious | None | None | None | None | I |
| R/Q | 0.5555 | ambiguous | 0.5086 | ambiguous | -0.017 | Destabilizing | 1.0 | D | 0.767 | deleterious | None | None | None | None | I |
| R/S | 0.9484 | likely_pathogenic | 0.9361 | pathogenic | -0.331 | Destabilizing | 1.0 | D | 0.719 | prob.delet. | N | 0.475096056 | None | None | I |
| R/T | 0.9318 | likely_pathogenic | 0.9079 | pathogenic | -0.118 | Destabilizing | 1.0 | D | 0.715 | prob.delet. | N | 0.507813405 | None | None | I |
| R/V | 0.9514 | likely_pathogenic | 0.9368 | pathogenic | 0.191 | Stabilizing | 1.0 | D | 0.753 | deleterious | None | None | None | None | I |
| R/W | 0.8493 | likely_pathogenic | 0.8052 | pathogenic | -0.429 | Destabilizing | 1.0 | D | 0.813 | deleterious | None | None | None | None | I |
| R/Y | 0.9593 | likely_pathogenic | 0.9459 | pathogenic | -0.022 | Destabilizing | 1.0 | D | 0.773 | 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.