Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 3378 | 10357;10358;10359 | chr2:178759155;178759154;178759153 | chr2:179623882;179623881;179623880 |
| N2AB | 3378 | 10357;10358;10359 | chr2:178759155;178759154;178759153 | chr2:179623882;179623881;179623880 |
| N2A | 3378 | 10357;10358;10359 | chr2:178759155;178759154;178759153 | chr2:179623882;179623881;179623880 |
| N2B | 3332 | 10219;10220;10221 | chr2:178759155;178759154;178759153 | chr2:179623882;179623881;179623880 |
| Novex-1 | 3332 | 10219;10220;10221 | chr2:178759155;178759154;178759153 | chr2:179623882;179623881;179623880 |
| Novex-2 | 3332 | 10219;10220;10221 | chr2:178759155;178759154;178759153 | chr2:179623882;179623881;179623880 |
| Novex-3 | 3378 | 10357;10358;10359 | chr2:178759155;178759154;178759153 | chr2:179623882;179623881;179623880 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/H | rs2088238170  |
None | 0.999 | D | 0.657 | 0.719 | 0.6603453 | 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 |
| Y/H | rs2088238170 |
None | 0.999 | D | 0.657 | 0.719 | 0.6603453 | gnomAD-4.0.0 | 6.5697E-06 | None | None | None | None | N | None | 0 | 6.54707E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| Y/S | rs1275007573 |
None | 0.999 | D | 0.699 | 0.65 | 0.80768555 | gnomAD-4.0.0 | 1.59086E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.02206E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/A | 0.8425 | likely_pathogenic | 0.8853 | pathogenic | -2.601 | Highly Destabilizing | 0.996 | D | 0.639 | neutral | None | None | None | None | N |
| Y/C | 0.475 | ambiguous | 0.495 | ambiguous | -1.188 | Destabilizing | 1.0 | D | 0.705 | prob.neutral | D | 0.7211438 | None | None | N |
| Y/D | 0.7507 | likely_pathogenic | 0.8298 | pathogenic | -1.327 | Destabilizing | 0.999 | D | 0.727 | prob.delet. | D | 0.66103876 | None | None | N |
| Y/E | 0.842 | likely_pathogenic | 0.9082 | pathogenic | -1.239 | Destabilizing | 1.0 | D | 0.709 | prob.delet. | None | None | None | None | N |
| Y/F | 0.0967 | likely_benign | 0.0936 | benign | -1.221 | Destabilizing | 0.217 | N | 0.226 | neutral | N | 0.48833543 | None | None | N |
| Y/G | 0.8113 | likely_pathogenic | 0.8411 | pathogenic | -2.917 | Highly Destabilizing | 1.0 | D | 0.699 | prob.neutral | None | None | None | None | N |
| Y/H | 0.2748 | likely_benign | 0.3426 | ambiguous | -1.243 | Destabilizing | 0.999 | D | 0.657 | neutral | D | 0.62145394 | None | None | N |
| Y/I | 0.6508 | likely_pathogenic | 0.7363 | pathogenic | -1.627 | Destabilizing | 0.998 | D | 0.661 | neutral | None | None | None | None | N |
| Y/K | 0.792 | likely_pathogenic | 0.8683 | pathogenic | -1.203 | Destabilizing | 1.0 | D | 0.703 | prob.neutral | None | None | None | None | N |
| Y/L | 0.6113 | likely_pathogenic | 0.6778 | pathogenic | -1.627 | Destabilizing | 0.983 | D | 0.539 | neutral | None | None | None | None | N |
| Y/M | 0.7586 | likely_pathogenic | 0.7957 | pathogenic | -1.264 | Destabilizing | 1.0 | D | 0.693 | prob.neutral | None | None | None | None | N |
| Y/N | 0.3972 | ambiguous | 0.4942 | ambiguous | -1.448 | Destabilizing | 0.999 | D | 0.72 | prob.delet. | D | 0.5975909 | None | None | N |
| Y/P | 0.9954 | likely_pathogenic | 0.9969 | pathogenic | -1.95 | Destabilizing | 1.0 | D | 0.729 | prob.delet. | None | None | None | None | N |
| Y/Q | 0.7096 | likely_pathogenic | 0.8139 | pathogenic | -1.467 | Destabilizing | 1.0 | D | 0.711 | prob.delet. | None | None | None | None | N |
| Y/R | 0.6545 | likely_pathogenic | 0.7585 | pathogenic | -0.654 | Destabilizing | 1.0 | D | 0.722 | prob.delet. | None | None | None | None | N |
| Y/S | 0.4909 | ambiguous | 0.5918 | pathogenic | -2.05 | Highly Destabilizing | 0.999 | D | 0.699 | prob.neutral | D | 0.52465427 | None | None | N |
| Y/T | 0.7195 | likely_pathogenic | 0.7734 | pathogenic | -1.868 | Destabilizing | 1.0 | D | 0.701 | prob.neutral | None | None | None | None | N |
| Y/V | 0.6053 | likely_pathogenic | 0.688 | pathogenic | -1.95 | Destabilizing | 0.992 | D | 0.605 | neutral | None | None | None | None | N |
| Y/W | 0.5872 | likely_pathogenic | 0.5898 | pathogenic | -0.701 | Destabilizing | 1.0 | D | 0.653 | neutral | 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.