Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27722 | 83389;83390;83391 | chr2:178562968;178562967;178562966 | chr2:179427695;179427694;179427693 |
| N2AB | 26081 | 78466;78467;78468 | chr2:178562968;178562967;178562966 | chr2:179427695;179427694;179427693 |
| N2A | 25154 | 75685;75686;75687 | chr2:178562968;178562967;178562966 | chr2:179427695;179427694;179427693 |
| N2B | 18657 | 56194;56195;56196 | chr2:178562968;178562967;178562966 | chr2:179427695;179427694;179427693 |
| Novex-1 | 18782 | 56569;56570;56571 | chr2:178562968;178562967;178562966 | chr2:179427695;179427694;179427693 |
| Novex-2 | 18849 | 56770;56771;56772 | chr2:178562968;178562967;178562966 | chr2:179427695;179427694;179427693 |
| 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 | 0.983 | N | 0.542 | 0.415 | 0.246773566709 | gnomAD-4.0.0 | 1.59152E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.8586E-06 | 0 | 0 |
| I/R | rs794729515  |
None | 0.983 | D | 0.738 | 0.673 | 0.89132661953 | gnomAD-4.0.0 | 6.84253E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99499E-07 | 0 | 0 |
| I/T | None | None | 0.892 | N | 0.547 | 0.495 | 0.767521279722 | gnomAD-4.0.0 | 2.73701E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.6985E-06 | 1.15934E-05 | 0 |
| I/V | None | None | 0.011 | N | 0.204 | 0.078 | 0.436239592564 | gnomAD-4.0.0 | 2.40064E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.625E-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 | 0.4706 | ambiguous | 0.542 | ambiguous | -1.869 | Destabilizing | 0.845 | D | 0.441 | neutral | None | None | None | None | I |
| I/C | 0.8543 | likely_pathogenic | 0.8881 | pathogenic | -1.057 | Destabilizing | 0.999 | D | 0.623 | neutral | None | None | None | None | I |
| I/D | 0.9531 | likely_pathogenic | 0.9649 | pathogenic | -1.696 | Destabilizing | 0.996 | D | 0.723 | prob.delet. | None | None | None | None | I |
| I/E | 0.7985 | likely_pathogenic | 0.835 | pathogenic | -1.616 | Destabilizing | 0.987 | D | 0.719 | prob.delet. | None | None | None | None | I |
| I/F | 0.3974 | ambiguous | 0.4468 | ambiguous | -1.185 | Destabilizing | 0.975 | D | 0.523 | neutral | None | None | None | None | I |
| I/G | 0.8874 | likely_pathogenic | 0.9196 | pathogenic | -2.256 | Highly Destabilizing | 0.987 | D | 0.711 | prob.delet. | None | None | None | None | I |
| I/H | 0.829 | likely_pathogenic | 0.8656 | pathogenic | -1.427 | Destabilizing | 0.999 | D | 0.739 | prob.delet. | None | None | None | None | I |
| I/K | 0.5927 | likely_pathogenic | 0.6313 | pathogenic | -1.423 | Destabilizing | 0.983 | D | 0.719 | prob.delet. | D | 0.529693335 | None | None | I |
| I/L | 0.2107 | likely_benign | 0.2443 | benign | -0.834 | Destabilizing | 0.426 | N | 0.358 | neutral | N | 0.500874204 | None | None | I |
| I/M | 0.1211 | likely_benign | 0.1367 | benign | -0.652 | Destabilizing | 0.983 | D | 0.542 | neutral | N | 0.502799988 | None | None | I |
| I/N | 0.6868 | likely_pathogenic | 0.7346 | pathogenic | -1.406 | Destabilizing | 0.996 | D | 0.737 | prob.delet. | None | None | None | None | I |
| I/P | 0.9324 | likely_pathogenic | 0.9355 | pathogenic | -1.152 | Destabilizing | 0.996 | D | 0.731 | prob.delet. | None | None | None | None | I |
| I/Q | 0.6646 | likely_pathogenic | 0.7222 | pathogenic | -1.489 | Destabilizing | 0.996 | D | 0.735 | prob.delet. | None | None | None | None | I |
| I/R | 0.516 | ambiguous | 0.5506 | ambiguous | -0.872 | Destabilizing | 0.983 | D | 0.738 | prob.delet. | D | 0.53373226 | None | None | I |
| I/S | 0.5797 | likely_pathogenic | 0.6523 | pathogenic | -1.989 | Destabilizing | 0.975 | D | 0.634 | neutral | None | None | None | None | I |
| I/T | 0.1909 | likely_benign | 0.2348 | benign | -1.785 | Destabilizing | 0.892 | D | 0.547 | neutral | N | 0.517323072 | None | None | I |
| I/V | 0.0883 | likely_benign | 0.1046 | benign | -1.152 | Destabilizing | 0.011 | N | 0.204 | neutral | N | 0.512449412 | None | None | I |
| I/W | 0.9034 | likely_pathogenic | 0.9194 | pathogenic | -1.37 | Destabilizing | 0.999 | D | 0.714 | prob.delet. | None | None | None | None | I |
| I/Y | 0.7692 | likely_pathogenic | 0.7956 | pathogenic | -1.112 | Destabilizing | 0.987 | D | 0.613 | 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.