Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28128 | 84607;84608;84609 | chr2:178561750;178561749;178561748 | chr2:179426477;179426476;179426475 |
| N2AB | 26487 | 79684;79685;79686 | chr2:178561750;178561749;178561748 | chr2:179426477;179426476;179426475 |
| N2A | 25560 | 76903;76904;76905 | chr2:178561750;178561749;178561748 | chr2:179426477;179426476;179426475 |
| N2B | 19063 | 57412;57413;57414 | chr2:178561750;178561749;178561748 | chr2:179426477;179426476;179426475 |
| Novex-1 | 19188 | 57787;57788;57789 | chr2:178561750;178561749;178561748 | chr2:179426477;179426476;179426475 |
| Novex-2 | 19255 | 57988;57989;57990 | chr2:178561750;178561749;178561748 | chr2:179426477;179426476;179426475 |
| 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/C | rs1375604948  |
None | 1.0 | D | 0.807 | 0.609 | 0.801244804775 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/C | rs1375604948 |
None | 1.0 | D | 0.807 | 0.609 | 0.801244804775 | gnomAD-4.0.0 | 1.23969E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.23334E-05 | None | 0 | 0 | 1.35635E-05 | 0 | 4.80354E-05 |
| R/G | rs1375604948 |
-2.348 | 1.0 | D | 0.728 | 0.587 | 0.751046792558 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| R/G | rs1375604948 |
-2.348 | 1.0 | D | 0.728 | 0.587 | 0.751046792558 | gnomAD-4.0.0 | 6.84391E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.15966E-05 | 0 |
| R/H | rs367596354 |
-2.289 | 1.0 | D | 0.805 | 0.554 | None | gnomAD-2.1.1 | 8.07E-06 | None | None | None | None | N | None | 6.46E-05 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| R/H | rs367596354 |
-2.289 | 1.0 | D | 0.805 | 0.554 | None | gnomAD-3.1.2 | 4.6E-05 | None | None | None | None | N | None | 7.24E-05 | 1.96361E-04 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.06954E-04 | 0 |
| R/H | rs367596354 |
-2.289 | 1.0 | D | 0.805 | 0.554 | None | gnomAD-4.0.0 | 1.05377E-05 | None | None | None | None | N | None | 9.34929E-05 | 1.16756E-04 | None | 0 | 2.23334E-05 | None | 0 | 0 | 8.47749E-07 | 1.09823E-05 | 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 | 0.9545 | likely_pathogenic | 0.9607 | pathogenic | -2.135 | Highly Destabilizing | 0.999 | D | 0.632 | neutral | None | None | None | None | N |
| R/C | 0.5497 | ambiguous | 0.5782 | pathogenic | -1.921 | Destabilizing | 1.0 | D | 0.807 | deleterious | D | 0.547654281 | None | None | N |
| R/D | 0.9971 | likely_pathogenic | 0.9973 | pathogenic | -1.371 | Destabilizing | 1.0 | D | 0.787 | deleterious | None | None | None | None | N |
| R/E | 0.9637 | likely_pathogenic | 0.9637 | pathogenic | -1.149 | Destabilizing | 0.999 | D | 0.665 | neutral | None | None | None | None | N |
| R/F | 0.9809 | likely_pathogenic | 0.9796 | pathogenic | -1.134 | Destabilizing | 1.0 | D | 0.836 | deleterious | None | None | None | None | N |
| R/G | 0.9392 | likely_pathogenic | 0.9481 | pathogenic | -2.444 | Highly Destabilizing | 1.0 | D | 0.728 | prob.delet. | D | 0.554148741 | None | None | N |
| R/H | 0.4719 | ambiguous | 0.4732 | ambiguous | -2.232 | Highly Destabilizing | 1.0 | D | 0.805 | deleterious | D | 0.565758536 | None | None | N |
| R/I | 0.9227 | likely_pathogenic | 0.9248 | pathogenic | -1.217 | Destabilizing | 1.0 | D | 0.821 | deleterious | None | None | None | None | N |
| R/K | 0.4115 | ambiguous | 0.4091 | ambiguous | -1.354 | Destabilizing | 0.998 | D | 0.657 | neutral | None | None | None | None | N |
| R/L | 0.8639 | likely_pathogenic | 0.8543 | pathogenic | -1.217 | Destabilizing | 1.0 | D | 0.728 | prob.delet. | D | 0.526258343 | None | None | N |
| R/M | 0.9248 | likely_pathogenic | 0.9266 | pathogenic | -1.744 | Destabilizing | 1.0 | D | 0.805 | deleterious | None | None | None | None | N |
| R/N | 0.9887 | likely_pathogenic | 0.9886 | pathogenic | -1.58 | Destabilizing | 1.0 | D | 0.764 | deleterious | None | None | None | None | N |
| R/P | 0.9987 | likely_pathogenic | 0.9986 | pathogenic | -1.517 | Destabilizing | 1.0 | D | 0.797 | deleterious | D | 0.566012025 | None | None | N |
| R/Q | 0.41 | ambiguous | 0.4097 | ambiguous | -1.29 | Destabilizing | 1.0 | D | 0.771 | deleterious | None | None | None | None | N |
| R/S | 0.9754 | likely_pathogenic | 0.9772 | pathogenic | -2.292 | Highly Destabilizing | 1.0 | D | 0.723 | prob.delet. | D | 0.526165756 | None | None | N |
| R/T | 0.96 | likely_pathogenic | 0.9627 | pathogenic | -1.878 | Destabilizing | 1.0 | D | 0.73 | prob.delet. | None | None | None | None | N |
| R/V | 0.9424 | likely_pathogenic | 0.943 | pathogenic | -1.517 | Destabilizing | 1.0 | D | 0.792 | deleterious | None | None | None | None | N |
| R/W | 0.8072 | likely_pathogenic | 0.8026 | pathogenic | -0.769 | Destabilizing | 1.0 | D | 0.787 | deleterious | None | None | None | None | N |
| R/Y | 0.9494 | likely_pathogenic | 0.9476 | pathogenic | -0.709 | Destabilizing | 1.0 | D | 0.829 | 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.