Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14046 | 42361;42362;42363 | chr2:178634738;178634737;178634736 | chr2:179499465;179499464;179499463 |
| N2AB | 12405 | 37438;37439;37440 | chr2:178634738;178634737;178634736 | chr2:179499465;179499464;179499463 |
| N2A | 11478 | 34657;34658;34659 | chr2:178634738;178634737;178634736 | chr2:179499465;179499464;179499463 |
| N2B | 4981 | 15166;15167;15168 | chr2:178634738;178634737;178634736 | chr2:179499465;179499464;179499463 |
| Novex-1 | 5106 | 15541;15542;15543 | chr2:178634738;178634737;178634736 | chr2:179499465;179499464;179499463 |
| Novex-2 | 5173 | 15742;15743;15744 | chr2:178634738;178634737;178634736 | chr2:179499465;179499464;179499463 |
| 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 | rs776291578  |
None | 0.915 | N | 0.567 | 0.242 | 0.511390160789 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| I/T | rs776291578 |
None | 0.915 | N | 0.567 | 0.242 | 0.511390160789 | gnomAD-4.0.0 | 3.71985E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.08737E-06 | 0 | 0 |
| I/V | None | None | 0.325 | N | 0.232 | 0.102 | 0.392702134506 | gnomAD-4.0.0 | 3.60097E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.9375E-06 | 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 | 0.8541 | likely_pathogenic | 0.7263 | pathogenic | -1.377 | Destabilizing | 0.745 | D | 0.537 | neutral | None | None | None | None | N |
| I/C | 0.9502 | likely_pathogenic | 0.8973 | pathogenic | -0.969 | Destabilizing | 0.998 | D | 0.613 | neutral | None | None | None | None | N |
| I/D | 0.9719 | likely_pathogenic | 0.9252 | pathogenic | -0.464 | Destabilizing | 0.994 | D | 0.761 | deleterious | None | None | None | None | N |
| I/E | 0.9423 | likely_pathogenic | 0.8673 | pathogenic | -0.479 | Destabilizing | 0.994 | D | 0.682 | prob.neutral | None | None | None | None | N |
| I/F | 0.4012 | ambiguous | 0.3006 | benign | -0.969 | Destabilizing | 0.949 | D | 0.469 | neutral | N | 0.434580959 | None | None | N |
| I/G | 0.9727 | likely_pathogenic | 0.9269 | pathogenic | -1.672 | Destabilizing | 0.981 | D | 0.664 | prob.neutral | None | None | None | None | N |
| I/H | 0.8868 | likely_pathogenic | 0.7462 | pathogenic | -0.828 | Destabilizing | 0.998 | D | 0.76 | deleterious | None | None | None | None | N |
| I/K | 0.8579 | likely_pathogenic | 0.6875 | pathogenic | -0.812 | Destabilizing | 0.981 | D | 0.659 | prob.neutral | None | None | None | None | N |
| I/L | 0.2833 | likely_benign | 0.2058 | benign | -0.662 | Destabilizing | 0.172 | N | 0.211 | neutral | N | 0.43296606 | None | None | N |
| I/M | 0.2668 | likely_benign | 0.1917 | benign | -0.573 | Destabilizing | 0.172 | N | 0.251 | neutral | N | 0.399309114 | None | None | N |
| I/N | 0.7658 | likely_pathogenic | 0.5784 | pathogenic | -0.624 | Destabilizing | 0.991 | D | 0.787 | deleterious | N | 0.429724964 | None | None | N |
| I/P | 0.984 | likely_pathogenic | 0.9605 | pathogenic | -0.867 | Destabilizing | 0.994 | D | 0.787 | deleterious | None | None | None | None | N |
| I/Q | 0.8903 | likely_pathogenic | 0.7363 | pathogenic | -0.801 | Destabilizing | 0.981 | D | 0.788 | deleterious | None | None | None | None | N |
| I/R | 0.8015 | likely_pathogenic | 0.5955 | pathogenic | -0.26 | Destabilizing | 0.981 | D | 0.781 | deleterious | None | None | None | None | N |
| I/S | 0.823 | likely_pathogenic | 0.6595 | pathogenic | -1.291 | Destabilizing | 0.915 | D | 0.646 | neutral | N | 0.432630093 | None | None | N |
| I/T | 0.7576 | likely_pathogenic | 0.6096 | pathogenic | -1.183 | Destabilizing | 0.915 | D | 0.567 | neutral | N | 0.430522815 | None | None | N |
| I/V | 0.1352 | likely_benign | 0.1284 | benign | -0.867 | Destabilizing | 0.325 | N | 0.232 | neutral | N | 0.432555899 | None | None | N |
| I/W | 0.9595 | likely_pathogenic | 0.9031 | pathogenic | -0.979 | Destabilizing | 0.998 | D | 0.773 | deleterious | None | None | None | None | N |
| I/Y | 0.8201 | likely_pathogenic | 0.6889 | pathogenic | -0.75 | Destabilizing | 0.994 | D | 0.637 | 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.