Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 33481 | 100666;100667;100668 | chr2:178536306;178536305;178536304 | chr2:179401033;179401032;179401031 |
| N2AB | 31840 | 95743;95744;95745 | chr2:178536306;178536305;178536304 | chr2:179401033;179401032;179401031 |
| N2A | 30913 | 92962;92963;92964 | chr2:178536306;178536305;178536304 | chr2:179401033;179401032;179401031 |
| N2B | 24416 | 73471;73472;73473 | chr2:178536306;178536305;178536304 | chr2:179401033;179401032;179401031 |
| Novex-1 | 24541 | 73846;73847;73848 | chr2:178536306;178536305;178536304 | chr2:179401033;179401032;179401031 |
| Novex-2 | 24608 | 74047;74048;74049 | chr2:178536306;178536305;178536304 | chr2:179401033;179401032;179401031 |
| 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 | 0.938 | N | 0.743 | 0.054 | 0.308278614506 | gnomAD-4.0.0 | 1.59165E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43308E-05 | 0 |
| I/T | rs1464925577  |
-2.554 | 0.007 | N | 0.552 | 0.133 | 0.382592752248 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 6.47E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/T | rs1464925577 |
-2.554 | 0.007 | N | 0.552 | 0.133 | 0.382592752248 | gnomAD-4.0.0 | 1.59165E-06 | None | None | None | None | N | None | 5.65611E-05 | 0 | 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 | 0.1828 | likely_benign | 0.1592 | benign | -2.147 | Highly Destabilizing | 0.37 | N | 0.752 | deleterious | None | None | None | None | N |
| I/C | 0.534 | ambiguous | 0.4715 | ambiguous | -1.217 | Destabilizing | 0.996 | D | 0.733 | deleterious | None | None | None | None | N |
| I/D | 0.4731 | ambiguous | 0.4281 | ambiguous | -1.578 | Destabilizing | 0.909 | D | 0.84 | deleterious | None | None | None | None | N |
| I/E | 0.3703 | ambiguous | 0.3544 | ambiguous | -1.509 | Destabilizing | 0.909 | D | 0.833 | deleterious | None | None | None | None | N |
| I/F | 0.2098 | likely_benign | 0.1878 | benign | -1.447 | Destabilizing | 0.953 | D | 0.808 | deleterious | None | None | None | None | N |
| I/G | 0.4571 | ambiguous | 0.4118 | ambiguous | -2.549 | Highly Destabilizing | 0.909 | D | 0.801 | deleterious | None | None | None | None | N |
| I/H | 0.5107 | ambiguous | 0.4508 | ambiguous | -1.702 | Destabilizing | 0.996 | D | 0.818 | deleterious | None | None | None | None | N |
| I/K | 0.2932 | likely_benign | 0.2803 | benign | -1.341 | Destabilizing | 0.883 | D | 0.835 | deleterious | N | 0.505144145 | None | None | N |
| I/L | 0.1447 | likely_benign | 0.1132 | benign | -1.066 | Destabilizing | 0.162 | N | 0.449 | neutral | N | 0.418274522 | None | None | N |
| I/M | 0.1286 | likely_benign | 0.1068 | benign | -0.803 | Destabilizing | 0.938 | D | 0.743 | deleterious | N | 0.465721752 | None | None | N |
| I/N | 0.1647 | likely_benign | 0.1384 | benign | -1.224 | Destabilizing | 0.909 | D | 0.85 | deleterious | None | None | None | None | N |
| I/P | 0.2839 | likely_benign | 0.2665 | benign | -1.399 | Destabilizing | 0.953 | D | 0.846 | deleterious | None | None | None | None | N |
| I/Q | 0.3636 | ambiguous | 0.3377 | benign | -1.35 | Destabilizing | 0.953 | D | 0.829 | deleterious | None | None | None | None | N |
| I/R | 0.2721 | likely_benign | 0.268 | benign | -0.785 | Destabilizing | 0.883 | D | 0.845 | deleterious | N | 0.478746978 | None | None | N |
| I/S | 0.1755 | likely_benign | 0.1601 | benign | -1.939 | Destabilizing | 0.587 | D | 0.78 | deleterious | None | None | None | None | N |
| I/T | 0.1326 | likely_benign | 0.1111 | benign | -1.745 | Destabilizing | 0.007 | N | 0.552 | neutral | N | 0.442324818 | None | None | N |
| I/V | 0.0772 | likely_benign | 0.0652 | benign | -1.399 | Destabilizing | 0.003 | N | 0.147 | neutral | N | 0.434820055 | None | None | N |
| I/W | 0.8003 | likely_pathogenic | 0.8058 | pathogenic | -1.563 | Destabilizing | 0.996 | D | 0.825 | deleterious | None | None | None | None | N |
| I/Y | 0.4908 | ambiguous | 0.4756 | ambiguous | -1.343 | Destabilizing | 0.984 | D | 0.792 | 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.