Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20310 | 61153;61154;61155 | chr2:178590797;178590796;178590795 | chr2:179455524;179455523;179455522 |
| N2AB | 18669 | 56230;56231;56232 | chr2:178590797;178590796;178590795 | chr2:179455524;179455523;179455522 |
| N2A | 17742 | 53449;53450;53451 | chr2:178590797;178590796;178590795 | chr2:179455524;179455523;179455522 |
| N2B | 11245 | 33958;33959;33960 | chr2:178590797;178590796;178590795 | chr2:179455524;179455523;179455522 |
| Novex-1 | 11370 | 34333;34334;34335 | chr2:178590797;178590796;178590795 | chr2:179455524;179455523;179455522 |
| Novex-2 | 11437 | 34534;34535;34536 | chr2:178590797;178590796;178590795 | chr2:179455524;179455523;179455522 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/C | rs200898955  |
-1.887 | 1.0 | N | 0.857 | 0.413 | None | gnomAD-2.1.1 | 7.17E-05 | None | None | None | None | N | None | 4.14E-05 | 0 | None | 0 | 7.22394E-04 | None | 9.89E-05 | None | 0 | 1.57E-05 | 0 |
| R/C | rs200898955 |
-1.887 | 1.0 | N | 0.857 | 0.413 | None | gnomAD-3.1.2 | 3.95E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 7.75194E-04 | None | 0 | 0 | 0 | 0 | 0 |
| R/C | rs200898955 |
-1.887 | 1.0 | N | 0.857 | 0.413 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 1E-03 | 0 | None | None | None | 0 | None |
| R/C | rs200898955 |
-1.887 | 1.0 | N | 0.857 | 0.413 | None | gnomAD-4.0.0 | 2.42707E-05 | None | None | None | None | N | None | 2.6713E-05 | 0 | None | 0 | 4.03895E-04 | None | 1.56504E-05 | 0 | 5.96074E-06 | 8.81193E-05 | 4.82532E-05 |
| R/H | rs569630571 |
-1.96 | 1.0 | N | 0.854 | 0.445 | 0.334659703779 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 0 | 2.91E-05 | None | 0 | 0 | None | 3.3E-05 | None | 0 | 8.92E-06 | 0 |
| R/H | rs569630571 |
-1.96 | 1.0 | N | 0.854 | 0.445 | 0.334659703779 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 3.16456E-03 | 0 | 0 | 0 |
| R/H | rs569630571 |
-1.96 | 1.0 | N | 0.854 | 0.445 | 0.334659703779 | gnomAD-4.0.0 | 1.55554E-05 | None | None | None | None | N | None | 1.33743E-05 | 1.67258E-05 | None | 0 | 0 | None | 1.56514E-05 | 3.30469E-04 | 1.27687E-05 | 2.20361E-05 | 4.82625E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.9266 | likely_pathogenic | 0.9289 | pathogenic | -1.992 | Destabilizing | 0.999 | D | 0.715 | prob.delet. | None | None | None | None | N |
| R/C | 0.3446 | ambiguous | 0.3587 | ambiguous | -1.96 | Destabilizing | 1.0 | D | 0.857 | deleterious | N | 0.475733197 | None | None | N |
| R/D | 0.992 | likely_pathogenic | 0.9906 | pathogenic | -1.294 | Destabilizing | 1.0 | D | 0.855 | deleterious | None | None | None | None | N |
| R/E | 0.8854 | likely_pathogenic | 0.8862 | pathogenic | -1.043 | Destabilizing | 0.999 | D | 0.733 | prob.delet. | None | None | None | None | N |
| R/F | 0.8558 | likely_pathogenic | 0.8614 | pathogenic | -1.113 | Destabilizing | 1.0 | D | 0.875 | deleterious | None | None | None | None | N |
| R/G | 0.8762 | likely_pathogenic | 0.8716 | pathogenic | -2.364 | Highly Destabilizing | 1.0 | D | 0.827 | deleterious | D | 0.522828616 | None | None | N |
| R/H | 0.2814 | likely_benign | 0.3049 | benign | -1.693 | Destabilizing | 1.0 | D | 0.854 | deleterious | N | 0.471684726 | None | None | N |
| R/I | 0.7251 | likely_pathogenic | 0.7095 | pathogenic | -0.897 | Destabilizing | 1.0 | D | 0.871 | deleterious | None | None | None | None | N |
| R/K | 0.1577 | likely_benign | 0.1818 | benign | -1.047 | Destabilizing | 0.998 | D | 0.641 | neutral | None | None | None | None | N |
| R/L | 0.6443 | likely_pathogenic | 0.6469 | pathogenic | -0.897 | Destabilizing | 1.0 | D | 0.827 | deleterious | N | 0.462882407 | None | None | N |
| R/M | 0.6084 | likely_pathogenic | 0.633 | pathogenic | -1.415 | Destabilizing | 1.0 | D | 0.84 | deleterious | None | None | None | None | N |
| R/N | 0.9684 | likely_pathogenic | 0.9657 | pathogenic | -1.606 | Destabilizing | 1.0 | D | 0.827 | deleterious | None | None | None | None | N |
| R/P | 0.9972 | likely_pathogenic | 0.9957 | pathogenic | -1.253 | Destabilizing | 1.0 | D | 0.86 | deleterious | N | 0.513008571 | None | None | N |
| R/Q | 0.2364 | likely_benign | 0.255 | benign | -1.415 | Destabilizing | 1.0 | D | 0.835 | deleterious | None | None | None | None | N |
| R/S | 0.9505 | likely_pathogenic | 0.9545 | pathogenic | -2.469 | Highly Destabilizing | 1.0 | D | 0.817 | deleterious | N | 0.465670792 | None | None | N |
| R/T | 0.8744 | likely_pathogenic | 0.8756 | pathogenic | -1.982 | Destabilizing | 1.0 | D | 0.816 | deleterious | None | None | None | None | N |
| R/V | 0.7922 | likely_pathogenic | 0.7885 | pathogenic | -1.253 | Destabilizing | 1.0 | D | 0.852 | deleterious | None | None | None | None | N |
| R/W | 0.4254 | ambiguous | 0.4083 | ambiguous | -0.585 | Destabilizing | 1.0 | D | 0.826 | deleterious | None | None | None | None | N |
| R/Y | 0.6699 | likely_pathogenic | 0.677 | pathogenic | -0.503 | Destabilizing | 1.0 | D | 0.875 | 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.