Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32407 | 97444;97445;97446 | chr2:178542537;178542536;178542535 | chr2:179407264;179407263;179407262 |
| N2AB | 30766 | 92521;92522;92523 | chr2:178542537;178542536;178542535 | chr2:179407264;179407263;179407262 |
| N2A | 29839 | 89740;89741;89742 | chr2:178542537;178542536;178542535 | chr2:179407264;179407263;179407262 |
| N2B | 23342 | 70249;70250;70251 | chr2:178542537;178542536;178542535 | chr2:179407264;179407263;179407262 |
| Novex-1 | 23467 | 70624;70625;70626 | chr2:178542537;178542536;178542535 | chr2:179407264;179407263;179407262 |
| Novex-2 | 23534 | 70825;70826;70827 | chr2:178542537;178542536;178542535 | chr2:179407264;179407263;179407262 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/M | None | None | 0.099 | N | 0.558 | 0.092 | 0.276065633971 | gnomAD-4.0.0 | 1.605E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.89367E-06 | 0 | 0 |
| I/N | None | None | 0.963 | N | 0.823 | 0.528 | 0.785320451344 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 6.07533E-05 | 0 |
| I/V | rs762555445  |
-1.543 | 0.001 | N | 0.192 | 0.076 | 0.210429274316 | gnomAD-2.1.1 | 8.11E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.8E-05 | 0 |
| I/V | rs762555445 |
-1.543 | 0.001 | N | 0.192 | 0.076 | 0.210429274316 | gnomAD-4.0.0 | 1.58022E-05 | None | None | None | None | N | None | 0 | 0 | None | 3.85238E-05 | 0 | None | 0 | 0 | 1.80666E-05 | 0 | 3.32812E-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 | 0.9005 | likely_pathogenic | 0.8592 | pathogenic | -2.199 | Highly Destabilizing | 0.25 | N | 0.711 | prob.delet. | None | None | None | None | N |
| I/C | 0.927 | likely_pathogenic | 0.8948 | pathogenic | -1.487 | Destabilizing | 0.977 | D | 0.742 | deleterious | None | None | None | None | N |
| I/D | 0.9974 | likely_pathogenic | 0.9968 | pathogenic | -2.215 | Highly Destabilizing | 0.972 | D | 0.821 | deleterious | None | None | None | None | N |
| I/E | 0.991 | likely_pathogenic | 0.989 | pathogenic | -2.028 | Highly Destabilizing | 0.92 | D | 0.808 | deleterious | None | None | None | None | N |
| I/F | 0.5368 | ambiguous | 0.4487 | ambiguous | -1.221 | Destabilizing | 0.81 | D | 0.771 | deleterious | N | 0.474571562 | None | None | N |
| I/G | 0.9869 | likely_pathogenic | 0.9804 | pathogenic | -2.713 | Highly Destabilizing | 0.92 | D | 0.817 | deleterious | None | None | None | None | N |
| I/H | 0.9928 | likely_pathogenic | 0.9896 | pathogenic | -2.188 | Highly Destabilizing | 0.992 | D | 0.805 | deleterious | None | None | None | None | N |
| I/K | 0.9873 | likely_pathogenic | 0.9846 | pathogenic | -1.654 | Destabilizing | 0.92 | D | 0.815 | deleterious | None | None | None | None | N |
| I/L | 0.1325 | likely_benign | 0.1225 | benign | -0.746 | Destabilizing | 0.099 | N | 0.519 | neutral | N | 0.425386922 | None | None | N |
| I/M | 0.1576 | likely_benign | 0.1413 | benign | -0.72 | Destabilizing | 0.099 | N | 0.558 | neutral | N | 0.477395946 | None | None | N |
| I/N | 0.9726 | likely_pathogenic | 0.9683 | pathogenic | -1.842 | Destabilizing | 0.963 | D | 0.823 | deleterious | N | 0.512643404 | None | None | N |
| I/P | 0.9498 | likely_pathogenic | 0.94 | pathogenic | -1.207 | Destabilizing | 0.972 | D | 0.825 | deleterious | None | None | None | None | N |
| I/Q | 0.9831 | likely_pathogenic | 0.9787 | pathogenic | -1.746 | Destabilizing | 0.92 | D | 0.82 | deleterious | None | None | None | None | N |
| I/R | 0.9827 | likely_pathogenic | 0.9783 | pathogenic | -1.386 | Destabilizing | 0.92 | D | 0.824 | deleterious | None | None | None | None | N |
| I/S | 0.9623 | likely_pathogenic | 0.9509 | pathogenic | -2.543 | Highly Destabilizing | 0.549 | D | 0.791 | deleterious | N | 0.489677304 | None | None | N |
| I/T | 0.9324 | likely_pathogenic | 0.9151 | pathogenic | -2.216 | Highly Destabilizing | 0.549 | D | 0.791 | deleterious | N | 0.519020306 | None | None | N |
| I/V | 0.0832 | likely_benign | 0.0741 | benign | -1.207 | Destabilizing | 0.001 | N | 0.192 | neutral | N | 0.397187174 | None | None | N |
| I/W | 0.9841 | likely_pathogenic | 0.9752 | pathogenic | -1.578 | Destabilizing | 0.992 | D | 0.806 | deleterious | None | None | None | None | N |
| I/Y | 0.9598 | likely_pathogenic | 0.9415 | pathogenic | -1.271 | Destabilizing | 0.92 | D | 0.796 | 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.