Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23508 | 70747;70748;70749 | chr2:178575610;178575609;178575608 | chr2:179440337;179440336;179440335 |
| N2AB | 21867 | 65824;65825;65826 | chr2:178575610;178575609;178575608 | chr2:179440337;179440336;179440335 |
| N2A | 20940 | 63043;63044;63045 | chr2:178575610;178575609;178575608 | chr2:179440337;179440336;179440335 |
| N2B | 14443 | 43552;43553;43554 | chr2:178575610;178575609;178575608 | chr2:179440337;179440336;179440335 |
| Novex-1 | 14568 | 43927;43928;43929 | chr2:178575610;178575609;178575608 | chr2:179440337;179440336;179440335 |
| Novex-2 | 14635 | 44128;44129;44130 | chr2:178575610;178575609;178575608 | chr2:179440337;179440336;179440335 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/G | rs1709797711  |
None | 1.0 | D | 0.748 | 0.609 | 0.586816528483 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/G | rs1709797711 |
None | 1.0 | D | 0.748 | 0.609 | 0.586816528483 | gnomAD-4.0.0 | 6.57358E-06 | None | None | None | None | N | None | 0 | 6.54879E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/I | rs1414118885 |
-0.476 | 1.0 | D | 0.826 | 0.608 | 0.769923350388 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.9E-06 | 0 |
| R/I | rs1414118885 |
-0.476 | 1.0 | D | 0.826 | 0.608 | 0.769923350388 | gnomAD-4.0.0 | 2.73711E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.59822E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.9794 | likely_pathogenic | 0.9875 | pathogenic | -1.552 | Destabilizing | 1.0 | D | 0.652 | neutral | None | None | None | None | N |
| R/C | 0.652 | likely_pathogenic | 0.7765 | pathogenic | -1.56 | Destabilizing | 1.0 | D | 0.807 | deleterious | None | None | None | None | N |
| R/D | 0.9984 | likely_pathogenic | 0.9989 | pathogenic | -0.72 | Destabilizing | 1.0 | D | 0.803 | deleterious | None | None | None | None | N |
| R/E | 0.9672 | likely_pathogenic | 0.9799 | pathogenic | -0.513 | Destabilizing | 0.999 | D | 0.699 | prob.neutral | None | None | None | None | N |
| R/F | 0.9951 | likely_pathogenic | 0.9963 | pathogenic | -0.777 | Destabilizing | 1.0 | D | 0.839 | deleterious | None | None | None | None | N |
| R/G | 0.9797 | likely_pathogenic | 0.9853 | pathogenic | -1.915 | Destabilizing | 1.0 | D | 0.748 | deleterious | D | 0.54377994 | None | None | N |
| R/H | 0.5759 | likely_pathogenic | 0.6412 | pathogenic | -1.819 | Destabilizing | 1.0 | D | 0.826 | deleterious | None | None | None | None | N |
| R/I | 0.9718 | likely_pathogenic | 0.9809 | pathogenic | -0.514 | Destabilizing | 1.0 | D | 0.826 | deleterious | D | 0.529790288 | None | None | N |
| R/K | 0.4813 | ambiguous | 0.5431 | ambiguous | -1.247 | Destabilizing | 0.995 | D | 0.673 | neutral | N | 0.506758055 | None | None | N |
| R/L | 0.943 | likely_pathogenic | 0.9525 | pathogenic | -0.514 | Destabilizing | 1.0 | D | 0.748 | deleterious | None | None | None | None | N |
| R/M | 0.9698 | likely_pathogenic | 0.9798 | pathogenic | -1.028 | Destabilizing | 1.0 | D | 0.813 | deleterious | None | None | None | None | N |
| R/N | 0.9931 | likely_pathogenic | 0.9955 | pathogenic | -1.146 | Destabilizing | 1.0 | D | 0.793 | deleterious | None | None | None | None | N |
| R/P | 0.9996 | likely_pathogenic | 0.9997 | pathogenic | -0.846 | Destabilizing | 1.0 | D | 0.811 | deleterious | None | None | None | None | N |
| R/Q | 0.457 | ambiguous | 0.5861 | pathogenic | -1.015 | Destabilizing | 1.0 | D | 0.795 | deleterious | None | None | None | None | N |
| R/S | 0.9853 | likely_pathogenic | 0.9913 | pathogenic | -1.97 | Destabilizing | 1.0 | D | 0.749 | deleterious | N | 0.511024016 | None | None | N |
| R/T | 0.9763 | likely_pathogenic | 0.9853 | pathogenic | -1.553 | Destabilizing | 1.0 | D | 0.756 | deleterious | N | 0.503390693 | None | None | N |
| R/V | 0.971 | likely_pathogenic | 0.9801 | pathogenic | -0.846 | Destabilizing | 1.0 | D | 0.803 | deleterious | None | None | None | None | N |
| R/W | 0.9201 | likely_pathogenic | 0.9384 | pathogenic | -0.339 | Destabilizing | 1.0 | D | 0.785 | deleterious | None | None | None | None | N |
| R/Y | 0.9802 | likely_pathogenic | 0.9852 | pathogenic | -0.154 | Destabilizing | 1.0 | D | 0.836 | 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.