Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27225 | 81898;81899;81900 | chr2:178564459;178564458;178564457 | chr2:179429186;179429185;179429184 |
| N2AB | 25584 | 76975;76976;76977 | chr2:178564459;178564458;178564457 | chr2:179429186;179429185;179429184 |
| N2A | 24657 | 74194;74195;74196 | chr2:178564459;178564458;178564457 | chr2:179429186;179429185;179429184 |
| N2B | 18160 | 54703;54704;54705 | chr2:178564459;178564458;178564457 | chr2:179429186;179429185;179429184 |
| Novex-1 | 18285 | 55078;55079;55080 | chr2:178564459;178564458;178564457 | chr2:179429186;179429185;179429184 |
| Novex-2 | 18352 | 55279;55280;55281 | chr2:178564459;178564458;178564457 | chr2:179429186;179429185;179429184 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/I | rs375211424  |
0.106 | 0.581 | N | 0.235 | 0.221 | None | gnomAD-2.1.1 | 8.36E-05 | None | None | None | None | N | None | 0 | 2.29634E-04 | None | 0 | 0 | None | 2.63591E-04 | None | 0 | 4.8E-05 | 1.4245E-04 |
| V/I | rs375211424 |
0.106 | 0.581 | N | 0.235 | 0.221 | None | gnomAD-3.1.2 | 1.77491E-04 | None | None | None | None | N | None | 7.24E-05 | 7.8637E-04 | 0 | 0 | 1.9305E-04 | None | 0 | 0 | 1.02959E-04 | 4.14422E-04 | 9.56023E-04 |
| V/I | rs375211424 |
0.106 | 0.581 | N | 0.235 | 0.221 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 1.4E-03 | None | None | 0 | 0 | None | None | None | 0 | None |
| V/I | rs375211424 |
0.106 | 0.581 | N | 0.235 | 0.221 | None | gnomAD-4.0.0 | 5.70667E-05 | None | None | None | None | N | None | 3.99904E-05 | 4.3538E-04 | None | 0 | 2.23934E-05 | None | 0 | 0 | 2.88393E-05 | 2.41891E-04 | 9.61415E-05 |
| V/L | None | None | 0.958 | D | 0.386 | 0.251 | 0.544128928594 | gnomAD-4.0.0 | 6.84972E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.00116E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.8601 | likely_pathogenic | 0.8187 | pathogenic | -1.246 | Destabilizing | 0.948 | D | 0.537 | neutral | N | 0.480470138 | None | None | N |
| V/C | 0.9116 | likely_pathogenic | 0.902 | pathogenic | -0.749 | Destabilizing | 1.0 | D | 0.71 | prob.delet. | None | None | None | None | N |
| V/D | 0.9848 | likely_pathogenic | 0.9773 | pathogenic | -1.04 | Destabilizing | 0.999 | D | 0.791 | deleterious | None | None | None | None | N |
| V/E | 0.9586 | likely_pathogenic | 0.9485 | pathogenic | -0.824 | Destabilizing | 0.999 | D | 0.727 | prob.delet. | N | 0.520121688 | None | None | N |
| V/F | 0.7979 | likely_pathogenic | 0.7499 | pathogenic | -0.605 | Destabilizing | 0.998 | D | 0.729 | prob.delet. | None | None | None | None | N |
| V/G | 0.9357 | likely_pathogenic | 0.9162 | pathogenic | -1.773 | Destabilizing | 0.999 | D | 0.778 | deleterious | N | 0.519614952 | None | None | N |
| V/H | 0.9827 | likely_pathogenic | 0.9778 | pathogenic | -1.586 | Destabilizing | 1.0 | D | 0.793 | deleterious | None | None | None | None | N |
| V/I | 0.0723 | likely_benign | 0.0736 | benign | 0.196 | Stabilizing | 0.581 | D | 0.235 | neutral | N | 0.454296824 | None | None | N |
| V/K | 0.9663 | likely_pathogenic | 0.964 | pathogenic | -0.648 | Destabilizing | 0.999 | D | 0.731 | prob.delet. | None | None | None | None | N |
| V/L | 0.528 | ambiguous | 0.5298 | ambiguous | 0.196 | Stabilizing | 0.958 | D | 0.386 | neutral | D | 0.52407941 | None | None | N |
| V/M | 0.5782 | likely_pathogenic | 0.54 | ambiguous | 0.017 | Stabilizing | 0.998 | D | 0.681 | prob.neutral | None | None | None | None | N |
| V/N | 0.9343 | likely_pathogenic | 0.9171 | pathogenic | -0.897 | Destabilizing | 0.999 | D | 0.813 | deleterious | None | None | None | None | N |
| V/P | 0.9817 | likely_pathogenic | 0.9792 | pathogenic | -0.254 | Destabilizing | 0.999 | D | 0.712 | prob.delet. | None | None | None | None | N |
| V/Q | 0.9523 | likely_pathogenic | 0.9456 | pathogenic | -0.682 | Destabilizing | 0.999 | D | 0.741 | deleterious | None | None | None | None | N |
| V/R | 0.9542 | likely_pathogenic | 0.9504 | pathogenic | -0.769 | Destabilizing | 0.999 | D | 0.811 | deleterious | None | None | None | None | N |
| V/S | 0.9161 | likely_pathogenic | 0.8827 | pathogenic | -1.606 | Destabilizing | 0.999 | D | 0.694 | prob.neutral | None | None | None | None | N |
| V/T | 0.8264 | likely_pathogenic | 0.7982 | pathogenic | -1.23 | Destabilizing | 0.992 | D | 0.629 | neutral | None | None | None | None | N |
| V/W | 0.9948 | likely_pathogenic | 0.9931 | pathogenic | -1.056 | Destabilizing | 1.0 | D | 0.748 | deleterious | None | None | None | None | N |
| V/Y | 0.9707 | likely_pathogenic | 0.9647 | pathogenic | -0.578 | Destabilizing | 0.999 | D | 0.724 | 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.