Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22721 | 68386;68387;68388 | chr2:178578869;178578868;178578867 | chr2:179443596;179443595;179443594 |
| N2AB | 21080 | 63463;63464;63465 | chr2:178578869;178578868;178578867 | chr2:179443596;179443595;179443594 |
| N2A | 20153 | 60682;60683;60684 | chr2:178578869;178578868;178578867 | chr2:179443596;179443595;179443594 |
| N2B | 13656 | 41191;41192;41193 | chr2:178578869;178578868;178578867 | chr2:179443596;179443595;179443594 |
| Novex-1 | 13781 | 41566;41567;41568 | chr2:178578869;178578868;178578867 | chr2:179443596;179443595;179443594 |
| Novex-2 | 13848 | 41767;41768;41769 | chr2:178578869;178578868;178578867 | chr2:179443596;179443595;179443594 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| E/K | rs374492812  |
-0.531 | 1.0 | N | 0.537 | 0.368 | None | gnomAD-2.1.1 | 1.18E-04 | None | None | None | None | N | None | 3.72055E-04 | 3.11509E-04 | None | 0 | 1.02902E-04 | None | 0 | None | 0 | 7.05E-05 | 2.81215E-04 |
| E/K | rs374492812 |
-0.531 | 1.0 | N | 0.537 | 0.368 | None | gnomAD-3.1.2 | 1.18393E-04 | None | None | None | None | N | None | 3.13858E-04 | 0 | 0 | 0 | 0 | None | 9.42E-05 | 0 | 4.41E-05 | 0 | 4.79846E-04 |
| E/K | rs374492812 |
-0.531 | 1.0 | N | 0.537 | 0.368 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 8E-04 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| E/K | rs374492812 |
-0.531 | 1.0 | N | 0.537 | 0.368 | None | gnomAD-4.0.0 | 1.03525E-04 | None | None | None | None | N | None | 2.13413E-04 | 1.83394E-04 | None | 0 | 2.23224E-05 | None | 9.37441E-05 | 1.65399E-04 | 1.05986E-04 | 1.0988E-05 | 9.60861E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| E/A | 0.6712 | likely_pathogenic | 0.6591 | pathogenic | -0.606 | Destabilizing | 0.999 | D | 0.673 | neutral | N | 0.507339088 | None | None | N |
| E/C | 0.9706 | likely_pathogenic | 0.972 | pathogenic | -0.468 | Destabilizing | 1.0 | D | 0.849 | deleterious | None | None | None | None | N |
| E/D | 0.9595 | likely_pathogenic | 0.9604 | pathogenic | -1.29 | Destabilizing | 0.999 | D | 0.459 | neutral | N | 0.490131376 | None | None | N |
| E/F | 0.9905 | likely_pathogenic | 0.9909 | pathogenic | -1.067 | Destabilizing | 1.0 | D | 0.88 | deleterious | None | None | None | None | N |
| E/G | 0.8025 | likely_pathogenic | 0.8223 | pathogenic | -0.895 | Destabilizing | 1.0 | D | 0.76 | deleterious | N | 0.501652266 | None | None | N |
| E/H | 0.9752 | likely_pathogenic | 0.975 | pathogenic | -1.26 | Destabilizing | 1.0 | D | 0.68 | prob.neutral | None | None | None | None | N |
| E/I | 0.9065 | likely_pathogenic | 0.8845 | pathogenic | 0.156 | Stabilizing | 1.0 | D | 0.888 | deleterious | None | None | None | None | N |
| E/K | 0.7103 | likely_pathogenic | 0.7465 | pathogenic | -0.493 | Destabilizing | 1.0 | D | 0.537 | neutral | N | 0.505069574 | None | None | N |
| E/L | 0.9584 | likely_pathogenic | 0.9575 | pathogenic | 0.156 | Stabilizing | 1.0 | D | 0.858 | deleterious | None | None | None | None | N |
| E/M | 0.8949 | likely_pathogenic | 0.889 | pathogenic | 0.584 | Stabilizing | 1.0 | D | 0.831 | deleterious | None | None | None | None | N |
| E/N | 0.9639 | likely_pathogenic | 0.9608 | pathogenic | -0.72 | Destabilizing | 1.0 | D | 0.726 | prob.delet. | None | None | None | None | N |
| E/P | 0.9988 | likely_pathogenic | 0.9991 | pathogenic | -0.077 | Destabilizing | 1.0 | D | 0.826 | deleterious | None | None | None | None | N |
| E/Q | 0.4037 | ambiguous | 0.361 | ambiguous | -0.626 | Destabilizing | 1.0 | D | 0.614 | neutral | N | 0.510206035 | None | None | N |
| E/R | 0.807 | likely_pathogenic | 0.8367 | pathogenic | -0.59 | Destabilizing | 1.0 | D | 0.727 | prob.delet. | None | None | None | None | N |
| E/S | 0.8213 | likely_pathogenic | 0.8077 | pathogenic | -1.111 | Destabilizing | 0.999 | D | 0.587 | neutral | None | None | None | None | N |
| E/T | 0.8496 | likely_pathogenic | 0.8258 | pathogenic | -0.845 | Destabilizing | 1.0 | D | 0.813 | deleterious | None | None | None | None | N |
| E/V | 0.7592 | likely_pathogenic | 0.7092 | pathogenic | -0.077 | Destabilizing | 1.0 | D | 0.825 | deleterious | N | 0.439145653 | None | None | N |
| E/W | 0.997 | likely_pathogenic | 0.9974 | pathogenic | -1.242 | Destabilizing | 1.0 | D | 0.851 | deleterious | None | None | None | None | N |
| E/Y | 0.9879 | likely_pathogenic | 0.989 | pathogenic | -0.871 | Destabilizing | 1.0 | D | 0.851 | 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.