Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17183 | 51772;51773;51774 | chr2:178609876;178609875;178609874 | chr2:179474603;179474602;179474601 |
| N2AB | 15542 | 46849;46850;46851 | chr2:178609876;178609875;178609874 | chr2:179474603;179474602;179474601 |
| N2A | 14615 | 44068;44069;44070 | chr2:178609876;178609875;178609874 | chr2:179474603;179474602;179474601 |
| N2B | 8118 | 24577;24578;24579 | chr2:178609876;178609875;178609874 | chr2:179474603;179474602;179474601 |
| Novex-1 | 8243 | 24952;24953;24954 | chr2:178609876;178609875;178609874 | chr2:179474603;179474602;179474601 |
| Novex-2 | 8310 | 25153;25154;25155 | chr2:178609876;178609875;178609874 | chr2:179474603;179474602;179474601 |
| 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/T | rs757000767  |
-3.228 | 0.939 | N | 0.678 | 0.336 | 0.615520507219 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 6.46E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/T | rs757000767 |
-3.228 | 0.939 | N | 0.678 | 0.336 | 0.615520507219 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 2.42E-05 | 6.57E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/T | rs757000767 |
-3.228 | 0.939 | N | 0.678 | 0.336 | 0.615520507219 | gnomAD-4.0.0 | 3.8477E-06 | None | None | None | None | N | None | 3.38914E-05 | 1.69624E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.9039 | likely_pathogenic | 0.8825 | pathogenic | -2.921 | Highly Destabilizing | 0.91 | D | 0.677 | prob.neutral | None | None | None | None | N |
| I/C | 0.8961 | likely_pathogenic | 0.879 | pathogenic | -2.096 | Highly Destabilizing | 0.999 | D | 0.697 | prob.neutral | None | None | None | None | N |
| I/D | 0.9844 | likely_pathogenic | 0.9787 | pathogenic | -3.494 | Highly Destabilizing | 0.998 | D | 0.775 | deleterious | None | None | None | None | N |
| I/E | 0.9528 | likely_pathogenic | 0.9409 | pathogenic | -3.285 | Highly Destabilizing | 0.993 | D | 0.749 | deleterious | None | None | None | None | N |
| I/F | 0.4524 | ambiguous | 0.4129 | ambiguous | -1.804 | Destabilizing | 0.982 | D | 0.697 | prob.neutral | N | 0.521135105 | None | None | N |
| I/G | 0.9817 | likely_pathogenic | 0.9739 | pathogenic | -3.412 | Highly Destabilizing | 0.993 | D | 0.743 | deleterious | None | None | None | None | N |
| I/H | 0.8568 | likely_pathogenic | 0.8388 | pathogenic | -2.816 | Highly Destabilizing | 0.999 | D | 0.755 | deleterious | None | None | None | None | N |
| I/K | 0.9166 | likely_pathogenic | 0.8953 | pathogenic | -2.435 | Highly Destabilizing | 0.993 | D | 0.747 | deleterious | None | None | None | None | N |
| I/L | 0.2851 | likely_benign | 0.2683 | benign | -1.486 | Destabilizing | 0.58 | D | 0.473 | neutral | N | 0.489292045 | None | None | N |
| I/M | 0.314 | likely_benign | 0.288 | benign | -1.385 | Destabilizing | 0.991 | D | 0.701 | prob.neutral | N | 0.487168862 | None | None | N |
| I/N | 0.7847 | likely_pathogenic | 0.7517 | pathogenic | -2.768 | Highly Destabilizing | 0.997 | D | 0.787 | deleterious | N | 0.473113077 | None | None | N |
| I/P | 0.9982 | likely_pathogenic | 0.9976 | pathogenic | -1.95 | Destabilizing | 0.998 | D | 0.779 | deleterious | None | None | None | None | N |
| I/Q | 0.9006 | likely_pathogenic | 0.8756 | pathogenic | -2.671 | Highly Destabilizing | 0.998 | D | 0.776 | deleterious | None | None | None | None | N |
| I/R | 0.8492 | likely_pathogenic | 0.8214 | pathogenic | -1.966 | Destabilizing | 0.993 | D | 0.783 | deleterious | None | None | None | None | N |
| I/S | 0.8447 | likely_pathogenic | 0.8102 | pathogenic | -3.361 | Highly Destabilizing | 0.991 | D | 0.665 | neutral | N | 0.470199788 | None | None | N |
| I/T | 0.7463 | likely_pathogenic | 0.7034 | pathogenic | -3.035 | Highly Destabilizing | 0.939 | D | 0.678 | prob.neutral | N | 0.500527759 | None | None | N |
| I/V | 0.1082 | likely_benign | 0.1058 | benign | -1.95 | Destabilizing | 0.02 | N | 0.256 | neutral | N | 0.495564657 | None | None | N |
| I/W | 0.9514 | likely_pathogenic | 0.9321 | pathogenic | -2.234 | Highly Destabilizing | 0.999 | D | 0.729 | prob.delet. | None | None | None | None | N |
| I/Y | 0.7872 | likely_pathogenic | 0.7538 | pathogenic | -2.016 | Highly Destabilizing | 0.993 | D | 0.709 | prob.delet. | 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.