Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26351 | 79276;79277;79278 | chr2:178567081;178567080;178567079 | chr2:179431808;179431807;179431806 |
| N2AB | 24710 | 74353;74354;74355 | chr2:178567081;178567080;178567079 | chr2:179431808;179431807;179431806 |
| N2A | 23783 | 71572;71573;71574 | chr2:178567081;178567080;178567079 | chr2:179431808;179431807;179431806 |
| N2B | 17286 | 52081;52082;52083 | chr2:178567081;178567080;178567079 | chr2:179431808;179431807;179431806 |
| Novex-1 | 17411 | 52456;52457;52458 | chr2:178567081;178567080;178567079 | chr2:179431808;179431807;179431806 |
| Novex-2 | 17478 | 52657;52658;52659 | chr2:178567081;178567080;178567079 | chr2:179431808;179431807;179431806 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/F | rs1706183837  |
None | 1.0 | D | 0.871 | 0.762 | 0.879023566714 | gnomAD-4.0.0 | 1.20034E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.66327E-05 |
| L/P | rs756625791 |
-1.908 | 1.0 | D | 0.857 | 0.881 | 0.954297974742 | gnomAD-2.1.1 | 2.01E-05 | None | None | None | None | N | None | 6.46E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 3.56E-05 | 0 |
| L/P | rs756625791 |
-1.908 | 1.0 | D | 0.857 | 0.881 | 0.954297974742 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| L/P | rs756625791 |
-1.908 | 1.0 | D | 0.857 | 0.881 | 0.954297974742 | gnomAD-4.0.0 | 5.76408E-05 | None | None | None | None | N | None | 1.33568E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 7.62958E-05 | 0 | 3.20297E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.9777 | likely_pathogenic | 0.9774 | pathogenic | -2.622 | Highly Destabilizing | 0.999 | D | 0.826 | deleterious | None | None | None | None | N |
| L/C | 0.9523 | likely_pathogenic | 0.9345 | pathogenic | -1.799 | Destabilizing | 1.0 | D | 0.79 | deleterious | None | None | None | None | N |
| L/D | 0.9997 | likely_pathogenic | 0.9997 | pathogenic | -2.87 | Highly Destabilizing | 1.0 | D | 0.861 | deleterious | None | None | None | None | N |
| L/E | 0.9989 | likely_pathogenic | 0.9989 | pathogenic | -2.673 | Highly Destabilizing | 1.0 | D | 0.855 | deleterious | None | None | None | None | N |
| L/F | 0.9227 | likely_pathogenic | 0.8952 | pathogenic | -1.655 | Destabilizing | 1.0 | D | 0.871 | deleterious | D | 0.664511912 | None | None | N |
| L/G | 0.9911 | likely_pathogenic | 0.9913 | pathogenic | -3.151 | Highly Destabilizing | 1.0 | D | 0.843 | deleterious | None | None | None | None | N |
| L/H | 0.9952 | likely_pathogenic | 0.9945 | pathogenic | -2.526 | Highly Destabilizing | 1.0 | D | 0.815 | deleterious | D | 0.681570655 | None | None | N |
| L/I | 0.6397 | likely_pathogenic | 0.6194 | pathogenic | -1.103 | Destabilizing | 0.999 | D | 0.833 | deleterious | D | 0.642375908 | None | None | N |
| L/K | 0.9969 | likely_pathogenic | 0.9972 | pathogenic | -1.976 | Destabilizing | 1.0 | D | 0.847 | deleterious | None | None | None | None | N |
| L/M | 0.5987 | likely_pathogenic | 0.5641 | pathogenic | -0.914 | Destabilizing | 1.0 | D | 0.845 | deleterious | None | None | None | None | N |
| L/N | 0.9957 | likely_pathogenic | 0.9958 | pathogenic | -2.229 | Highly Destabilizing | 1.0 | D | 0.867 | deleterious | None | None | None | None | N |
| L/P | 0.9971 | likely_pathogenic | 0.9968 | pathogenic | -1.59 | Destabilizing | 1.0 | D | 0.857 | deleterious | D | 0.681570655 | None | None | N |
| L/Q | 0.9935 | likely_pathogenic | 0.9934 | pathogenic | -2.159 | Highly Destabilizing | 1.0 | D | 0.86 | deleterious | None | None | None | None | N |
| L/R | 0.9939 | likely_pathogenic | 0.9941 | pathogenic | -1.577 | Destabilizing | 1.0 | D | 0.853 | deleterious | D | 0.665319129 | None | None | N |
| L/S | 0.9975 | likely_pathogenic | 0.9974 | pathogenic | -2.928 | Highly Destabilizing | 1.0 | D | 0.848 | deleterious | None | None | None | None | N |
| L/T | 0.9894 | likely_pathogenic | 0.9887 | pathogenic | -2.589 | Highly Destabilizing | 1.0 | D | 0.84 | deleterious | None | None | None | None | N |
| L/V | 0.6958 | likely_pathogenic | 0.6534 | pathogenic | -1.59 | Destabilizing | 0.999 | D | 0.841 | deleterious | D | 0.599304006 | None | None | N |
| L/W | 0.9938 | likely_pathogenic | 0.9919 | pathogenic | -2.032 | Highly Destabilizing | 1.0 | D | 0.775 | deleterious | None | None | None | None | N |
| L/Y | 0.9908 | likely_pathogenic | 0.9875 | pathogenic | -1.763 | Destabilizing | 1.0 | D | 0.829 | 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.