Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21720 | 65383;65384;65385 | chr2:178584393;178584392;178584391 | chr2:179449120;179449119;179449118 |
| N2AB | 20079 | 60460;60461;60462 | chr2:178584393;178584392;178584391 | chr2:179449120;179449119;179449118 |
| N2A | 19152 | 57679;57680;57681 | chr2:178584393;178584392;178584391 | chr2:179449120;179449119;179449118 |
| N2B | 12655 | 38188;38189;38190 | chr2:178584393;178584392;178584391 | chr2:179449120;179449119;179449118 |
| Novex-1 | 12780 | 38563;38564;38565 | chr2:178584393;178584392;178584391 | chr2:179449120;179449119;179449118 |
| Novex-2 | 12847 | 38764;38765;38766 | chr2:178584393;178584392;178584391 | chr2:179449120;179449119;179449118 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/T | rs776953525  |
-0.97 | 0.198 | N | 0.318 | 0.268 | 0.339555952218 | gnomAD-2.1.1 | 2.42E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 5.35E-05 | 0 |
| P/T | rs776953525 |
-0.97 | 0.198 | N | 0.318 | 0.268 | 0.339555952218 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| P/T | rs776953525 |
-0.97 | 0.198 | N | 0.318 | 0.268 | 0.339555952218 | gnomAD-4.0.0 | 1.15367E-05 | None | None | None | None | N | None | 1.69222E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.91566E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.1345 | likely_benign | 0.1165 | benign | -1.229 | Destabilizing | 0.978 | D | 0.545 | neutral | N | 0.467473978 | None | None | N |
| P/C | 0.7309 | likely_pathogenic | 0.6638 | pathogenic | -0.575 | Destabilizing | 1.0 | D | 0.735 | prob.delet. | None | None | None | None | N |
| P/D | 0.9083 | likely_pathogenic | 0.9041 | pathogenic | -0.936 | Destabilizing | 0.998 | D | 0.653 | neutral | None | None | None | None | N |
| P/E | 0.7253 | likely_pathogenic | 0.6853 | pathogenic | -0.93 | Destabilizing | 0.998 | D | 0.649 | neutral | None | None | None | None | N |
| P/F | 0.8619 | likely_pathogenic | 0.8262 | pathogenic | -0.952 | Destabilizing | 0.999 | D | 0.748 | deleterious | None | None | None | None | N |
| P/G | 0.6101 | likely_pathogenic | 0.5546 | ambiguous | -1.531 | Destabilizing | 0.992 | D | 0.632 | neutral | None | None | None | None | N |
| P/H | 0.5233 | ambiguous | 0.4391 | ambiguous | -1.007 | Destabilizing | 1.0 | D | 0.725 | prob.delet. | N | 0.499258323 | None | None | N |
| P/I | 0.6121 | likely_pathogenic | 0.5488 | ambiguous | -0.504 | Destabilizing | 0.995 | D | 0.752 | deleterious | None | None | None | None | N |
| P/K | 0.7126 | likely_pathogenic | 0.6285 | pathogenic | -0.904 | Destabilizing | 0.995 | D | 0.66 | neutral | None | None | None | None | N |
| P/L | 0.3376 | likely_benign | 0.2931 | benign | -0.504 | Destabilizing | 0.978 | D | 0.673 | neutral | N | 0.45086973 | None | None | N |
| P/M | 0.66 | likely_pathogenic | 0.6036 | pathogenic | -0.355 | Destabilizing | 1.0 | D | 0.727 | prob.delet. | None | None | None | None | N |
| P/N | 0.7607 | likely_pathogenic | 0.7068 | pathogenic | -0.674 | Destabilizing | 0.998 | D | 0.733 | prob.delet. | None | None | None | None | N |
| P/Q | 0.4345 | ambiguous | 0.3449 | ambiguous | -0.814 | Destabilizing | 0.999 | D | 0.694 | prob.neutral | None | None | None | None | N |
| P/R | 0.4629 | ambiguous | 0.3614 | ambiguous | -0.424 | Destabilizing | 0.997 | D | 0.738 | prob.delet. | N | 0.392957577 | None | None | N |
| P/S | 0.3044 | likely_benign | 0.2628 | benign | -1.162 | Destabilizing | 0.956 | D | 0.54 | neutral | N | 0.454198037 | None | None | N |
| P/T | 0.2671 | likely_benign | 0.2382 | benign | -1.043 | Destabilizing | 0.198 | N | 0.318 | neutral | N | 0.357857995 | None | None | N |
| P/V | 0.4176 | ambiguous | 0.3677 | ambiguous | -0.711 | Destabilizing | 0.983 | D | 0.625 | neutral | None | None | None | None | N |
| P/W | 0.9155 | likely_pathogenic | 0.8909 | pathogenic | -1.151 | Destabilizing | 1.0 | D | 0.693 | prob.neutral | None | None | None | None | N |
| P/Y | 0.7838 | likely_pathogenic | 0.7344 | pathogenic | -0.839 | Destabilizing | 0.999 | D | 0.748 | deleterious | 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.