Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2233 | 6922;6923;6924 | chr2:178775014;178775013;178775012 | chr2:179639741;179639740;179639739 |
| N2AB | 2233 | 6922;6923;6924 | chr2:178775014;178775013;178775012 | chr2:179639741;179639740;179639739 |
| N2A | 2233 | 6922;6923;6924 | chr2:178775014;178775013;178775012 | chr2:179639741;179639740;179639739 |
| N2B | 2187 | 6784;6785;6786 | chr2:178775014;178775013;178775012 | chr2:179639741;179639740;179639739 |
| Novex-1 | 2187 | 6784;6785;6786 | chr2:178775014;178775013;178775012 | chr2:179639741;179639740;179639739 |
| Novex-2 | 2187 | 6784;6785;6786 | chr2:178775014;178775013;178775012 | chr2:179639741;179639740;179639739 |
| Novex-3 | 2233 | 6922;6923;6924 | chr2:178775014;178775013;178775012 | chr2:179639741;179639740;179639739 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/T | rs1364650008  |
-2.655 | 0.012 | D | 0.522 | 0.495 | 0.746771168191 | gnomAD-2.1.1 | 7.96E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 6.53E-05 | None | 0 | 0 | 0 |
| I/T | rs1364650008 |
-2.655 | 0.012 | D | 0.522 | 0.495 | 0.746771168191 | gnomAD-4.0.0 | 4.7726E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 4.29849E-05 | 0 |
| I/V | rs1574638831 |
None | None | N | 0.257 | 0.273 | 0.308278614506 | gnomAD-4.0.0 | 2.05239E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99339E-07 | 0 | 3.31181E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.8121 | likely_pathogenic | 0.7958 | pathogenic | -2.885 | Highly Destabilizing | 0.007 | N | 0.436 | neutral | None | None | None | None | N |
| I/C | 0.8886 | likely_pathogenic | 0.8718 | pathogenic | -2.028 | Highly Destabilizing | 0.356 | N | 0.745 | deleterious | None | None | None | None | N |
| I/D | 0.9898 | likely_pathogenic | 0.9903 | pathogenic | -3.454 | Highly Destabilizing | 0.016 | N | 0.703 | prob.neutral | None | None | None | None | N |
| I/E | 0.9773 | likely_pathogenic | 0.9796 | pathogenic | -3.125 | Highly Destabilizing | None | N | 0.547 | neutral | None | None | None | None | N |
| I/F | 0.5116 | ambiguous | 0.5169 | ambiguous | -1.768 | Destabilizing | 0.072 | N | 0.617 | neutral | None | None | None | None | N |
| I/G | 0.9687 | likely_pathogenic | 0.9664 | pathogenic | -3.508 | Highly Destabilizing | 0.072 | N | 0.712 | prob.delet. | None | None | None | None | N |
| I/H | 0.9597 | likely_pathogenic | 0.9602 | pathogenic | -3.227 | Highly Destabilizing | 0.356 | N | 0.819 | deleterious | None | None | None | None | N |
| I/K | 0.9498 | likely_pathogenic | 0.9561 | pathogenic | -2.151 | Highly Destabilizing | 0.012 | N | 0.701 | prob.neutral | D | 0.712524983 | None | None | N |
| I/L | 0.1864 | likely_benign | 0.1839 | benign | -1.006 | Destabilizing | 0.002 | N | 0.331 | neutral | D | 0.545998815 | None | None | N |
| I/M | 0.257 | likely_benign | 0.2549 | benign | -1.145 | Destabilizing | 0.171 | N | 0.631 | neutral | D | 0.677118339 | None | None | N |
| I/N | 0.8856 | likely_pathogenic | 0.891 | pathogenic | -2.858 | Highly Destabilizing | 0.072 | N | 0.761 | deleterious | None | None | None | None | N |
| I/P | 0.9907 | likely_pathogenic | 0.9895 | pathogenic | -1.623 | Destabilizing | 0.136 | N | 0.745 | deleterious | None | None | None | None | N |
| I/Q | 0.9572 | likely_pathogenic | 0.9595 | pathogenic | -2.491 | Highly Destabilizing | 0.038 | N | 0.749 | deleterious | None | None | None | None | N |
| I/R | 0.93 | likely_pathogenic | 0.9374 | pathogenic | -2.207 | Highly Destabilizing | 0.055 | N | 0.763 | deleterious | D | 0.712524983 | None | None | N |
| I/S | 0.8665 | likely_pathogenic | 0.8628 | pathogenic | -3.442 | Highly Destabilizing | 0.031 | N | 0.681 | prob.neutral | None | None | None | None | N |
| I/T | 0.8065 | likely_pathogenic | 0.7944 | pathogenic | -2.945 | Highly Destabilizing | 0.012 | N | 0.522 | neutral | D | 0.604669072 | None | None | N |
| I/V | 0.0676 | likely_benign | 0.0645 | benign | -1.623 | Destabilizing | None | N | 0.257 | neutral | N | 0.483552761 | None | None | N |
| I/W | 0.9849 | likely_pathogenic | 0.9841 | pathogenic | -2.187 | Highly Destabilizing | 0.864 | D | 0.812 | deleterious | None | None | None | None | N |
| I/Y | 0.9066 | likely_pathogenic | 0.9126 | pathogenic | -1.978 | Destabilizing | 0.136 | N | 0.713 | 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.