Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22438 | 67537;67538;67539 | chr2:178579975;178579974;178579973 | chr2:179444702;179444701;179444700 |
| N2AB | 20797 | 62614;62615;62616 | chr2:178579975;178579974;178579973 | chr2:179444702;179444701;179444700 |
| N2A | 19870 | 59833;59834;59835 | chr2:178579975;178579974;178579973 | chr2:179444702;179444701;179444700 |
| N2B | 13373 | 40342;40343;40344 | chr2:178579975;178579974;178579973 | chr2:179444702;179444701;179444700 |
| Novex-1 | 13498 | 40717;40718;40719 | chr2:178579975;178579974;178579973 | chr2:179444702;179444701;179444700 |
| Novex-2 | 13565 | 40918;40919;40920 | chr2:178579975;178579974;178579973 | chr2:179444702;179444701;179444700 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/E | rs911744113  |
None | 0.011 | N | 0.203 | 0.077 | 0.0806252709748 | gnomAD-4.0.0 | 3.18504E-06 | None | None | None | None | I | None | 0 | 2.28718E-05 | None | 0 | 0 | None | 0 | 0 | 2.86028E-06 | 0 | 0 |
| D/N | rs755558410 |
-0.61 | 0.892 | N | 0.628 | 0.275 | 0.33440975612 | gnomAD-2.1.1 | 8.06E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 6.54E-05 | None | 0 | 0 | 0 |
| D/N | rs755558410 |
-0.61 | 0.892 | N | 0.628 | 0.275 | 0.33440975612 | gnomAD-4.0.0 | 1.36887E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.31932E-05 | 0 |
| D/Y | None | None | 0.994 | N | 0.726 | 0.468 | 0.333651784274 | gnomAD-4.0.0 | 6.84436E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99669E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.2206 | likely_benign | 0.2624 | benign | -0.681 | Destabilizing | 0.892 | D | 0.564 | neutral | N | 0.434612198 | None | None | I |
| D/C | 0.6693 | likely_pathogenic | 0.7256 | pathogenic | -0.315 | Destabilizing | 0.999 | D | 0.755 | deleterious | None | None | None | None | I |
| D/E | 0.1184 | likely_benign | 0.1267 | benign | -0.607 | Destabilizing | 0.011 | N | 0.203 | neutral | N | 0.330042249 | None | None | I |
| D/F | 0.6017 | likely_pathogenic | 0.6764 | pathogenic | -0.113 | Destabilizing | 0.996 | D | 0.727 | prob.delet. | None | None | None | None | I |
| D/G | 0.3851 | ambiguous | 0.4496 | ambiguous | -1.051 | Destabilizing | 0.892 | D | 0.597 | neutral | N | 0.499450324 | None | None | I |
| D/H | 0.4044 | ambiguous | 0.4918 | ambiguous | -0.349 | Destabilizing | 0.995 | D | 0.626 | neutral | N | 0.514401134 | None | None | I |
| D/I | 0.2668 | likely_benign | 0.3301 | benign | 0.309 | Stabilizing | 0.987 | D | 0.711 | prob.delet. | None | None | None | None | I |
| D/K | 0.4019 | ambiguous | 0.5311 | ambiguous | -0.412 | Destabilizing | 0.845 | D | 0.553 | neutral | None | None | None | None | I |
| D/L | 0.3063 | likely_benign | 0.3763 | ambiguous | 0.309 | Stabilizing | 0.975 | D | 0.673 | neutral | None | None | None | None | I |
| D/M | 0.5597 | ambiguous | 0.6175 | pathogenic | 0.728 | Stabilizing | 0.999 | D | 0.718 | prob.delet. | None | None | None | None | I |
| D/N | 0.1601 | likely_benign | 0.1787 | benign | -0.919 | Destabilizing | 0.892 | D | 0.628 | neutral | N | 0.488177324 | None | None | I |
| D/P | 0.6882 | likely_pathogenic | 0.7644 | pathogenic | 0.004 | Stabilizing | 0.987 | D | 0.622 | neutral | None | None | None | None | I |
| D/Q | 0.3481 | ambiguous | 0.4232 | ambiguous | -0.767 | Destabilizing | 0.95 | D | 0.589 | neutral | None | None | None | None | I |
| D/R | 0.5172 | ambiguous | 0.637 | pathogenic | -0.176 | Destabilizing | 0.975 | D | 0.655 | neutral | None | None | None | None | I |
| D/S | 0.1942 | likely_benign | 0.2125 | benign | -1.205 | Destabilizing | 0.916 | D | 0.528 | neutral | None | None | None | None | I |
| D/T | 0.309 | likely_benign | 0.3598 | ambiguous | -0.894 | Destabilizing | 0.975 | D | 0.586 | neutral | None | None | None | None | I |
| D/V | 0.1737 | likely_benign | 0.2188 | benign | 0.004 | Stabilizing | 0.983 | D | 0.661 | neutral | N | 0.419317459 | None | None | I |
| D/W | 0.9209 | likely_pathogenic | 0.9463 | pathogenic | 0.14 | Stabilizing | 0.999 | D | 0.721 | prob.delet. | None | None | None | None | I |
| D/Y | 0.2595 | likely_benign | 0.345 | ambiguous | 0.155 | Stabilizing | 0.994 | D | 0.726 | prob.delet. | N | 0.50728316 | 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.