Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2256 | 6991;6992;6993 | chr2:178774945;178774944;178774943 | chr2:179639672;179639671;179639670 |
| N2AB | 2256 | 6991;6992;6993 | chr2:178774945;178774944;178774943 | chr2:179639672;179639671;179639670 |
| N2A | 2256 | 6991;6992;6993 | chr2:178774945;178774944;178774943 | chr2:179639672;179639671;179639670 |
| N2B | 2210 | 6853;6854;6855 | chr2:178774945;178774944;178774943 | chr2:179639672;179639671;179639670 |
| Novex-1 | 2210 | 6853;6854;6855 | chr2:178774945;178774944;178774943 | chr2:179639672;179639671;179639670 |
| Novex-2 | 2210 | 6853;6854;6855 | chr2:178774945;178774944;178774943 | chr2:179639672;179639671;179639670 |
| Novex-3 | 2256 | 6991;6992;6993 | chr2:178774945;178774944;178774943 | chr2:179639672;179639671;179639670 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | rs1385805778  |
-1.225 | 0.981 | N | 0.579 | 0.281 | 0.279776271856 | gnomAD-2.1.1 | 3.99E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| T/M | rs780758720 |
-0.213 | 1.0 | D | 0.834 | 0.548 | None | gnomAD-2.1.1 | 1.77E-05 | None | None | None | None | N | None | 0 | 2.83E-05 | None | 0 | 0 | None | 0 | None | 0 | 3.11E-05 | 0 |
| T/M | rs780758720 |
-0.213 | 1.0 | D | 0.834 | 0.548 | None | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 4.41E-05 | 0 | 0 |
| T/M | rs780758720 |
-0.213 | 1.0 | D | 0.834 | 0.548 | None | gnomAD-4.0.0 | 2.72676E-05 | None | None | None | None | N | None | 0 | 1.66728E-05 | None | 0 | 2.23045E-05 | None | 0 | 0 | 3.05114E-05 | 0 | 9.6043E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.3971 | ambiguous | 0.428 | ambiguous | -1.111 | Destabilizing | 0.981 | D | 0.579 | neutral | N | 0.494210754 | None | None | N |
| T/C | 0.8663 | likely_pathogenic | 0.8678 | pathogenic | -0.588 | Destabilizing | 1.0 | D | 0.838 | deleterious | None | None | None | None | N |
| T/D | 0.9612 | likely_pathogenic | 0.967 | pathogenic | -0.43 | Destabilizing | 0.999 | D | 0.783 | deleterious | None | None | None | None | N |
| T/E | 0.9643 | likely_pathogenic | 0.969 | pathogenic | -0.337 | Destabilizing | 0.999 | D | 0.769 | deleterious | None | None | None | None | N |
| T/F | 0.9676 | likely_pathogenic | 0.9692 | pathogenic | -0.832 | Destabilizing | 1.0 | D | 0.893 | deleterious | None | None | None | None | N |
| T/G | 0.7577 | likely_pathogenic | 0.7688 | pathogenic | -1.466 | Destabilizing | 0.997 | D | 0.733 | prob.delet. | None | None | None | None | N |
| T/H | 0.9254 | likely_pathogenic | 0.9264 | pathogenic | -1.52 | Destabilizing | 1.0 | D | 0.868 | deleterious | None | None | None | None | N |
| T/I | 0.9257 | likely_pathogenic | 0.9321 | pathogenic | -0.217 | Destabilizing | 1.0 | D | 0.851 | deleterious | None | None | None | None | N |
| T/K | 0.9417 | likely_pathogenic | 0.9452 | pathogenic | -0.629 | Destabilizing | 1.0 | D | 0.774 | deleterious | D | 0.687764896 | None | None | N |
| T/L | 0.7646 | likely_pathogenic | 0.7755 | pathogenic | -0.217 | Destabilizing | 0.998 | D | 0.703 | prob.neutral | None | None | None | None | N |
| T/M | 0.4997 | ambiguous | 0.5096 | ambiguous | -0.02 | Destabilizing | 1.0 | D | 0.834 | deleterious | D | 0.69740043 | None | None | N |
| T/N | 0.6536 | likely_pathogenic | 0.6755 | pathogenic | -0.818 | Destabilizing | 0.999 | D | 0.683 | prob.neutral | None | None | None | None | N |
| T/P | 0.9703 | likely_pathogenic | 0.9699 | pathogenic | -0.482 | Destabilizing | 0.999 | D | 0.851 | deleterious | D | 0.69740043 | None | None | N |
| T/Q | 0.9147 | likely_pathogenic | 0.9207 | pathogenic | -0.826 | Destabilizing | 1.0 | D | 0.858 | deleterious | None | None | None | None | N |
| T/R | 0.9421 | likely_pathogenic | 0.9446 | pathogenic | -0.545 | Destabilizing | 1.0 | D | 0.853 | deleterious | D | 0.695979279 | None | None | N |
| T/S | 0.2557 | likely_benign | 0.2647 | benign | -1.187 | Destabilizing | 0.905 | D | 0.353 | neutral | N | 0.495412034 | None | None | N |
| T/V | 0.7812 | likely_pathogenic | 0.794 | pathogenic | -0.482 | Destabilizing | 0.998 | D | 0.572 | neutral | None | None | None | None | N |
| T/W | 0.9925 | likely_pathogenic | 0.9922 | pathogenic | -0.77 | Destabilizing | 1.0 | D | 0.859 | deleterious | None | None | None | None | N |
| T/Y | 0.9655 | likely_pathogenic | 0.9661 | pathogenic | -0.524 | Destabilizing | 1.0 | D | 0.887 | 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.