Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14473 | 43642;43643;43644 | chr2:178632589;178632588;178632587 | chr2:179497316;179497315;179497314 |
| N2AB | 12832 | 38719;38720;38721 | chr2:178632589;178632588;178632587 | chr2:179497316;179497315;179497314 |
| N2A | 11905 | 35938;35939;35940 | chr2:178632589;178632588;178632587 | chr2:179497316;179497315;179497314 |
| N2B | 5408 | 16447;16448;16449 | chr2:178632589;178632588;178632587 | chr2:179497316;179497315;179497314 |
| Novex-1 | 5533 | 16822;16823;16824 | chr2:178632589;178632588;178632587 | chr2:179497316;179497315;179497314 |
| Novex-2 | 5600 | 17023;17024;17025 | chr2:178632589;178632588;178632587 | chr2:179497316;179497315;179497314 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/G | None | None | 1.0 | D | 0.789 | 0.863 | 0.704013138179 | gnomAD-4.0.0 | 4.80129E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.25001E-06 | 0 | 0 |
| D/H | rs397517573  |
0.276 | 1.0 | D | 0.834 | 0.649 | 0.700962985929 | gnomAD-2.1.1 | 2.39722E-04 | None | None | None | None | N | None | 0 | 0 | None | 4.7453E-03 | 0 | None | 0 | None | 0 | 1.09799E-04 | 5.6243E-04 |
| D/H | rs397517573 |
0.276 | 1.0 | D | 0.834 | 0.649 | 0.700962985929 | gnomAD-3.1.2 | 1.1839E-04 | None | None | None | None | N | None | 0 | 0 | 0 | 4.03691E-03 | 0 | None | 0 | 0 | 4.41E-05 | 0 | 4.79386E-04 |
| D/H | rs397517573 |
0.276 | 1.0 | D | 0.834 | 0.649 | 0.700962985929 | gnomAD-4.0.0 | 1.16535E-04 | None | None | None | None | N | None | 0 | 0 | None | 4.32637E-03 | 0 | None | 0 | 0 | 3.05201E-05 | 1.09808E-05 | 3.68436E-04 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.9456 | likely_pathogenic | 0.8626 | pathogenic | 0.783 | Stabilizing | 1.0 | D | 0.841 | deleterious | D | 0.751999021 | None | None | N |
| D/C | 0.989 | likely_pathogenic | 0.9764 | pathogenic | 0.549 | Stabilizing | 1.0 | D | 0.823 | deleterious | None | None | None | None | N |
| D/E | 0.8716 | likely_pathogenic | 0.7603 | pathogenic | -0.627 | Destabilizing | 1.0 | D | 0.561 | neutral | D | 0.753096497 | None | None | N |
| D/F | 0.9837 | likely_pathogenic | 0.9622 | pathogenic | 1.473 | Stabilizing | 1.0 | D | 0.85 | deleterious | None | None | None | None | N |
| D/G | 0.9294 | likely_pathogenic | 0.8507 | pathogenic | 0.301 | Stabilizing | 1.0 | D | 0.789 | deleterious | D | 0.751247667 | None | None | N |
| D/H | 0.9304 | likely_pathogenic | 0.8788 | pathogenic | 1.097 | Stabilizing | 1.0 | D | 0.834 | deleterious | D | 0.67801749 | None | None | N |
| D/I | 0.9869 | likely_pathogenic | 0.9658 | pathogenic | 2.071 | Highly Stabilizing | 1.0 | D | 0.843 | deleterious | None | None | None | None | N |
| D/K | 0.987 | likely_pathogenic | 0.9745 | pathogenic | 0.491 | Stabilizing | 1.0 | D | 0.83 | deleterious | None | None | None | None | N |
| D/L | 0.9765 | likely_pathogenic | 0.9416 | pathogenic | 2.071 | Highly Stabilizing | 1.0 | D | 0.842 | deleterious | None | None | None | None | N |
| D/M | 0.988 | likely_pathogenic | 0.97 | pathogenic | 2.335 | Highly Stabilizing | 1.0 | D | 0.809 | deleterious | None | None | None | None | N |
| D/N | 0.7167 | likely_pathogenic | 0.5662 | pathogenic | -0.393 | Destabilizing | 1.0 | D | 0.793 | deleterious | D | 0.753530745 | None | None | N |
| D/P | 0.9992 | likely_pathogenic | 0.9985 | pathogenic | 1.674 | Stabilizing | 1.0 | D | 0.843 | deleterious | None | None | None | None | N |
| D/Q | 0.9788 | likely_pathogenic | 0.9533 | pathogenic | -0.025 | Destabilizing | 1.0 | D | 0.786 | deleterious | None | None | None | None | N |
| D/R | 0.9914 | likely_pathogenic | 0.9823 | pathogenic | 0.454 | Stabilizing | 1.0 | D | 0.852 | deleterious | None | None | None | None | N |
| D/S | 0.9049 | likely_pathogenic | 0.7984 | pathogenic | -0.638 | Destabilizing | 1.0 | D | 0.769 | deleterious | None | None | None | None | N |
| D/T | 0.9753 | likely_pathogenic | 0.9345 | pathogenic | -0.192 | Destabilizing | 1.0 | D | 0.833 | deleterious | None | None | None | None | N |
| D/V | 0.9549 | likely_pathogenic | 0.8942 | pathogenic | 1.674 | Stabilizing | 1.0 | D | 0.842 | deleterious | D | 0.751237294 | None | None | N |
| D/W | 0.9954 | likely_pathogenic | 0.9905 | pathogenic | 1.445 | Stabilizing | 1.0 | D | 0.809 | deleterious | None | None | None | None | N |
| D/Y | 0.845 | likely_pathogenic | 0.7383 | pathogenic | 1.75 | Stabilizing | 1.0 | D | 0.849 | deleterious | D | 0.751323028 | 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.