Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 34177 | 102754;102755;102756 | chr2:178534086;178534085;178534084 | chr2:179398813;179398812;179398811 |
| N2AB | 32536 | 97831;97832;97833 | chr2:178534086;178534085;178534084 | chr2:179398813;179398812;179398811 |
| N2A | 31609 | 95050;95051;95052 | chr2:178534086;178534085;178534084 | chr2:179398813;179398812;179398811 |
| N2B | 25112 | 75559;75560;75561 | chr2:178534086;178534085;178534084 | chr2:179398813;179398812;179398811 |
| Novex-1 | 25237 | 75934;75935;75936 | chr2:178534086;178534085;178534084 | chr2:179398813;179398812;179398811 |
| Novex-2 | 25304 | 76135;76136;76137 | chr2:178534086;178534085;178534084 | chr2:179398813;179398812;179398811 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/M | rs760034286  |
-0.785 | 1.0 | N | 0.781 | 0.587 | 0.663037096684 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | I | None | 0 | 2.9E-05 | None | 0 | 1.11272E-04 | None | 0 | None | 0 | 0 | 0 |
| L/M | rs760034286 |
-0.785 | 1.0 | N | 0.781 | 0.587 | 0.663037096684 | gnomAD-4.0.0 | 1.59102E-06 | None | None | None | None | I | None | 0 | 2.28645E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| L/V | None | None | 0.999 | D | 0.533 | 0.511 | 0.54963036629 | gnomAD-4.0.0 | 1.59102E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43271E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.9188 | likely_pathogenic | 0.9093 | pathogenic | -2.136 | Highly Destabilizing | 0.999 | D | 0.713 | prob.delet. | None | None | None | None | I |
| L/C | 0.9619 | likely_pathogenic | 0.9612 | pathogenic | -1.215 | Destabilizing | 1.0 | D | 0.833 | deleterious | None | None | None | None | I |
| L/D | 0.9985 | likely_pathogenic | 0.9983 | pathogenic | -2.576 | Highly Destabilizing | 1.0 | D | 0.906 | deleterious | None | None | None | None | I |
| L/E | 0.985 | likely_pathogenic | 0.9827 | pathogenic | -2.305 | Highly Destabilizing | 1.0 | D | 0.904 | deleterious | None | None | None | None | I |
| L/F | 0.8116 | likely_pathogenic | 0.8176 | pathogenic | -1.277 | Destabilizing | 1.0 | D | 0.759 | deleterious | None | None | None | None | I |
| L/G | 0.9901 | likely_pathogenic | 0.9874 | pathogenic | -2.685 | Highly Destabilizing | 1.0 | D | 0.902 | deleterious | None | None | None | None | I |
| L/H | 0.9833 | likely_pathogenic | 0.9805 | pathogenic | -2.195 | Highly Destabilizing | 1.0 | D | 0.879 | deleterious | None | None | None | None | I |
| L/I | 0.1581 | likely_benign | 0.1639 | benign | -0.533 | Destabilizing | 0.999 | D | 0.557 | neutral | None | None | None | None | I |
| L/K | 0.9676 | likely_pathogenic | 0.964 | pathogenic | -1.609 | Destabilizing | 1.0 | D | 0.876 | deleterious | None | None | None | None | I |
| L/M | 0.3434 | ambiguous | 0.3466 | ambiguous | -0.454 | Destabilizing | 1.0 | D | 0.781 | deleterious | N | 0.512215099 | None | None | I |
| L/N | 0.9914 | likely_pathogenic | 0.99 | pathogenic | -2.131 | Highly Destabilizing | 1.0 | D | 0.909 | deleterious | None | None | None | None | I |
| L/P | 0.9884 | likely_pathogenic | 0.9876 | pathogenic | -1.052 | Destabilizing | 1.0 | D | 0.908 | deleterious | N | 0.513229057 | None | None | I |
| L/Q | 0.9619 | likely_pathogenic | 0.9557 | pathogenic | -1.899 | Destabilizing | 1.0 | D | 0.896 | deleterious | D | 0.531586802 | None | None | I |
| L/R | 0.9566 | likely_pathogenic | 0.9498 | pathogenic | -1.528 | Destabilizing | 1.0 | D | 0.893 | deleterious | D | 0.531333312 | None | None | I |
| L/S | 0.991 | likely_pathogenic | 0.9893 | pathogenic | -2.75 | Highly Destabilizing | 1.0 | D | 0.867 | deleterious | None | None | None | None | I |
| L/T | 0.934 | likely_pathogenic | 0.9254 | pathogenic | -2.326 | Highly Destabilizing | 1.0 | D | 0.805 | deleterious | None | None | None | None | I |
| L/V | 0.2379 | likely_benign | 0.2481 | benign | -1.052 | Destabilizing | 0.999 | D | 0.533 | neutral | D | 0.533755764 | None | None | I |
| L/W | 0.9601 | likely_pathogenic | 0.9579 | pathogenic | -1.688 | Destabilizing | 1.0 | D | 0.803 | deleterious | None | None | None | None | I |
| L/Y | 0.9744 | likely_pathogenic | 0.9726 | pathogenic | -1.318 | Destabilizing | 1.0 | D | 0.871 | deleterious | None | None | None | None | I |
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.