Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30899 | 92920;92921;92922 | chr2:178548931;178548930;178548929 | chr2:179413658;179413657;179413656 |
| N2AB | 29258 | 87997;87998;87999 | chr2:178548931;178548930;178548929 | chr2:179413658;179413657;179413656 |
| N2A | 28331 | 85216;85217;85218 | chr2:178548931;178548930;178548929 | chr2:179413658;179413657;179413656 |
| N2B | 21834 | 65725;65726;65727 | chr2:178548931;178548930;178548929 | chr2:179413658;179413657;179413656 |
| Novex-1 | 21959 | 66100;66101;66102 | chr2:178548931;178548930;178548929 | chr2:179413658;179413657;179413656 |
| Novex-2 | 22026 | 66301;66302;66303 | chr2:178548931;178548930;178548929 | chr2:179413658;179413657;179413656 |
| 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 | rs373727636  |
-2.124 | 0.062 | N | 0.547 | 0.3 | None | gnomAD-2.1.1 | 2.2483E-04 | None | None | None | None | I | None | 0 | 0 | None | 9.66E-05 | 0 | None | 0 | None | 0 | 4.76309E-04 | 1.40489E-04 |
| I/T | rs373727636 |
-2.124 | 0.062 | N | 0.547 | 0.3 | None | gnomAD-3.1.2 | 1.70826E-04 | None | None | None | None | I | None | 4.82E-05 | 0 | 0 | 2.88018E-04 | 0 | None | 0 | 0 | 3.23377E-04 | 0 | 4.77555E-04 |
| I/T | rs373727636 |
-2.124 | 0.062 | N | 0.547 | 0.3 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | I | None | 0 | 0 | None | None | 0 | 1E-03 | None | None | None | 0 | None |
| I/T | rs373727636 |
-2.124 | 0.062 | N | 0.547 | 0.3 | None | gnomAD-4.0.0 | 2.15622E-04 | None | None | None | None | I | None | 2.66454E-05 | 0 | None | 3.37838E-05 | 0 | None | 0 | 1.64962E-04 | 2.83089E-04 | 0 | 1.60041E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.3134 | likely_benign | 0.3607 | ambiguous | -2.169 | Highly Destabilizing | 0.035 | N | 0.424 | neutral | None | None | None | None | I |
| I/C | 0.5351 | ambiguous | 0.5972 | pathogenic | -1.595 | Destabilizing | 0.824 | D | 0.547 | neutral | None | None | None | None | I |
| I/D | 0.8145 | likely_pathogenic | 0.8549 | pathogenic | -1.889 | Destabilizing | 0.555 | D | 0.638 | neutral | None | None | None | None | I |
| I/E | 0.5902 | likely_pathogenic | 0.6493 | pathogenic | -1.789 | Destabilizing | 0.555 | D | 0.634 | neutral | None | None | None | None | I |
| I/F | 0.1684 | likely_benign | 0.1972 | benign | -1.363 | Destabilizing | 0.317 | N | 0.577 | neutral | N | 0.517788155 | None | None | I |
| I/G | 0.6313 | likely_pathogenic | 0.7196 | pathogenic | -2.587 | Highly Destabilizing | 0.262 | N | 0.621 | neutral | None | None | None | None | I |
| I/H | 0.603 | likely_pathogenic | 0.672 | pathogenic | -1.791 | Destabilizing | 0.935 | D | 0.627 | neutral | None | None | None | None | I |
| I/K | 0.4612 | ambiguous | 0.5294 | ambiguous | -1.503 | Destabilizing | 0.555 | D | 0.633 | neutral | None | None | None | None | I |
| I/L | 0.0904 | likely_benign | 0.1001 | benign | -1.03 | Destabilizing | 0.005 | N | 0.339 | neutral | N | 0.453659319 | None | None | I |
| I/M | 0.0859 | likely_benign | 0.095 | benign | -1.006 | Destabilizing | 0.317 | N | 0.563 | neutral | N | 0.504570929 | None | None | I |
| I/N | 0.4159 | ambiguous | 0.4783 | ambiguous | -1.513 | Destabilizing | 0.741 | D | 0.625 | neutral | D | 0.523330048 | None | None | I |
| I/P | 0.9514 | likely_pathogenic | 0.9692 | pathogenic | -1.384 | Destabilizing | 0.791 | D | 0.641 | neutral | None | None | None | None | I |
| I/Q | 0.452 | ambiguous | 0.5152 | ambiguous | -1.591 | Destabilizing | 0.791 | D | 0.647 | neutral | None | None | None | None | I |
| I/R | 0.3779 | ambiguous | 0.4498 | ambiguous | -1.02 | Destabilizing | 0.555 | D | 0.63 | neutral | None | None | None | None | I |
| I/S | 0.3308 | likely_benign | 0.3808 | ambiguous | -2.234 | Highly Destabilizing | 0.117 | N | 0.569 | neutral | N | 0.505571007 | None | None | I |
| I/T | 0.2139 | likely_benign | 0.2511 | benign | -2.01 | Highly Destabilizing | 0.062 | N | 0.547 | neutral | N | 0.470380998 | None | None | I |
| I/V | 0.0545 | likely_benign | 0.0578 | benign | -1.384 | Destabilizing | None | N | 0.141 | neutral | N | 0.360820942 | None | None | I |
| I/W | 0.7868 | likely_pathogenic | 0.8298 | pathogenic | -1.524 | Destabilizing | 0.935 | D | 0.663 | neutral | None | None | None | None | I |
| I/Y | 0.5356 | ambiguous | 0.6134 | pathogenic | -1.285 | Destabilizing | 0.555 | D | 0.588 | neutral | 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.