Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 33725 | 101398;101399;101400 | chr2:178535442;178535441;178535440 | chr2:179400169;179400168;179400167 |
| N2AB | 32084 | 96475;96476;96477 | chr2:178535442;178535441;178535440 | chr2:179400169;179400168;179400167 |
| N2A | 31157 | 93694;93695;93696 | chr2:178535442;178535441;178535440 | chr2:179400169;179400168;179400167 |
| N2B | 24660 | 74203;74204;74205 | chr2:178535442;178535441;178535440 | chr2:179400169;179400168;179400167 |
| Novex-1 | 24785 | 74578;74579;74580 | chr2:178535442;178535441;178535440 | chr2:179400169;179400168;179400167 |
| Novex-2 | 24852 | 74779;74780;74781 | chr2:178535442;178535441;178535440 | chr2:179400169;179400168;179400167 |
| 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/F | None | None | 0.999 | D | 0.704 | 0.366 | 0.629718971361 | gnomAD-4.0.0 | 6.84188E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99441E-07 | 0 | 0 |
| I/T | rs1329737429  |
-2.815 | 0.46 | N | 0.524 | 0.231 | 0.618703310563 | gnomAD-2.1.1 | 7.14E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.56E-05 | 0 |
| I/T | rs1329737429 |
-2.815 | 0.46 | N | 0.524 | 0.231 | 0.618703310563 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| I/T | rs1329737429 |
-2.815 | 0.46 | N | 0.524 | 0.231 | 0.618703310563 | gnomAD-4.0.0 | 5.57685E-06 | None | None | None | None | N | None | 0 | 1.66667E-05 | None | 0 | 0 | None | 0 | 1.64366E-04 | 5.08544E-06 | 0 | 1.60108E-05 |
| I/V | rs878900245 |
-1.741 | 0.425 | N | 0.395 | 0.182 | None | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 1.77E-05 | 0 |
| I/V | rs878900245 |
-1.741 | 0.425 | N | 0.395 | 0.182 | None | 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 |
| I/V | rs878900245 |
-1.741 | 0.425 | N | 0.395 | 0.182 | None | gnomAD-4.0.0 | 1.92088E-05 | None | None | None | None | N | None | 1.3344E-05 | 1.66672E-05 | None | 0 | 0 | None | 0 | 0 | 2.37319E-05 | 0 | 1.60092E-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 | 0.785 | likely_pathogenic | 0.7215 | pathogenic | -2.7 | Highly Destabilizing | 0.993 | D | 0.677 | prob.neutral | None | None | None | None | N |
| I/C | 0.9182 | likely_pathogenic | 0.9063 | pathogenic | -1.974 | Destabilizing | 1.0 | D | 0.681 | prob.neutral | None | None | None | None | N |
| I/D | 0.9823 | likely_pathogenic | 0.9704 | pathogenic | -3.145 | Highly Destabilizing | 1.0 | D | 0.744 | deleterious | None | None | None | None | N |
| I/E | 0.9445 | likely_pathogenic | 0.9242 | pathogenic | -2.965 | Highly Destabilizing | 1.0 | D | 0.739 | prob.delet. | None | None | None | None | N |
| I/F | 0.4135 | ambiguous | 0.377 | ambiguous | -1.638 | Destabilizing | 0.999 | D | 0.704 | prob.neutral | D | 0.522751258 | None | None | N |
| I/G | 0.9741 | likely_pathogenic | 0.958 | pathogenic | -3.184 | Highly Destabilizing | 0.999 | D | 0.739 | prob.delet. | None | None | None | None | N |
| I/H | 0.8688 | likely_pathogenic | 0.8317 | pathogenic | -2.525 | Highly Destabilizing | 1.0 | D | 0.738 | prob.delet. | None | None | None | None | N |
| I/K | 0.874 | likely_pathogenic | 0.8498 | pathogenic | -2.133 | Highly Destabilizing | 0.999 | D | 0.742 | deleterious | None | None | None | None | N |
| I/L | 0.2879 | likely_benign | 0.2833 | benign | -1.313 | Destabilizing | 0.173 | N | 0.432 | neutral | N | 0.500605117 | None | None | N |
| I/M | 0.2463 | likely_benign | 0.2367 | benign | -1.27 | Destabilizing | 0.989 | D | 0.683 | prob.neutral | N | 0.487662614 | None | None | N |
| I/N | 0.826 | likely_pathogenic | 0.7661 | pathogenic | -2.38 | Highly Destabilizing | 1.0 | D | 0.739 | prob.delet. | N | 0.469985978 | None | None | N |
| I/P | 0.9971 | likely_pathogenic | 0.9961 | pathogenic | -1.757 | Destabilizing | 1.0 | D | 0.75 | deleterious | None | None | None | None | N |
| I/Q | 0.8739 | likely_pathogenic | 0.838 | pathogenic | -2.338 | Highly Destabilizing | 1.0 | D | 0.763 | deleterious | None | None | None | None | N |
| I/R | 0.7835 | likely_pathogenic | 0.7373 | pathogenic | -1.663 | Destabilizing | 1.0 | D | 0.747 | deleterious | None | None | None | None | N |
| I/S | 0.7744 | likely_pathogenic | 0.68 | pathogenic | -3.011 | Highly Destabilizing | 0.991 | D | 0.707 | prob.neutral | N | 0.512859551 | None | None | N |
| I/T | 0.4143 | ambiguous | 0.3453 | ambiguous | -2.708 | Highly Destabilizing | 0.46 | N | 0.524 | neutral | N | 0.488406611 | None | None | N |
| I/V | 0.1062 | likely_benign | 0.1067 | benign | -1.757 | Destabilizing | 0.425 | N | 0.395 | neutral | N | 0.473207872 | None | None | N |
| I/W | 0.9327 | likely_pathogenic | 0.9184 | pathogenic | -2.007 | Highly Destabilizing | 1.0 | D | 0.735 | prob.delet. | None | None | None | None | N |
| I/Y | 0.8325 | likely_pathogenic | 0.7961 | pathogenic | -1.774 | Destabilizing | 0.996 | D | 0.685 | prob.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.