Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15210 | 45853;45854;45855 | chr2:178620982;178620981;178620980 | chr2:179485709;179485708;179485707 |
| N2AB | 13569 | 40930;40931;40932 | chr2:178620982;178620981;178620980 | chr2:179485709;179485708;179485707 |
| N2A | 12642 | 38149;38150;38151 | chr2:178620982;178620981;178620980 | chr2:179485709;179485708;179485707 |
| N2B | 6145 | 18658;18659;18660 | chr2:178620982;178620981;178620980 | chr2:179485709;179485708;179485707 |
| Novex-1 | 6270 | 19033;19034;19035 | chr2:178620982;178620981;178620980 | chr2:179485709;179485708;179485707 |
| Novex-2 | 6337 | 19234;19235;19236 | chr2:178620982;178620981;178620980 | chr2:179485709;179485708;179485707 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/M | None | None | 0.999 | D | 0.711 | 0.53 | 0.554356711338 | gnomAD-4.0.0 | 1.37185E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.8007E-06 | 0 | 0 |
| I/N | rs193086479  |
-2.389 | 0.999 | D | 0.861 | 0.732 | None | gnomAD-2.1.1 | 4.08E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.68E-05 | None | 0 | None | 0 | 0 | 0 |
| I/N | rs193086479 |
-2.389 | 0.999 | D | 0.861 | 0.732 | None | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.94628E-04 | None | 0 | 0 | 0 | 0 | 0 |
| I/N | rs193086479 |
-2.389 | 0.999 | D | 0.861 | 0.732 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 1E-03 | 0 | None | None | None | 0 | None |
| I/N | rs193086479 |
-2.389 | 0.999 | D | 0.861 | 0.732 | None | gnomAD-4.0.0 | 6.57808E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.95084E-04 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | None | None | 0.333 | N | 0.205 | 0.153 | 0.40218521252 | gnomAD-4.0.0 | 1.37187E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.80071E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.6746 | likely_pathogenic | 0.5792 | pathogenic | -1.978 | Destabilizing | 0.992 | D | 0.693 | prob.neutral | None | None | None | None | N |
| I/C | 0.8988 | likely_pathogenic | 0.8387 | pathogenic | -1.173 | Destabilizing | 1.0 | D | 0.761 | deleterious | None | None | None | None | N |
| I/D | 0.9746 | likely_pathogenic | 0.9516 | pathogenic | -1.773 | Destabilizing | 1.0 | D | 0.865 | deleterious | None | None | None | None | N |
| I/E | 0.9396 | likely_pathogenic | 0.8973 | pathogenic | -1.708 | Destabilizing | 1.0 | D | 0.865 | deleterious | None | None | None | None | N |
| I/F | 0.3194 | likely_benign | 0.2757 | benign | -1.236 | Destabilizing | 0.998 | D | 0.745 | deleterious | N | 0.501706648 | None | None | N |
| I/G | 0.9398 | likely_pathogenic | 0.9035 | pathogenic | -2.365 | Highly Destabilizing | 1.0 | D | 0.861 | deleterious | None | None | None | None | N |
| I/H | 0.9376 | likely_pathogenic | 0.8891 | pathogenic | -1.653 | Destabilizing | 1.0 | D | 0.832 | deleterious | None | None | None | None | N |
| I/K | 0.8943 | likely_pathogenic | 0.8259 | pathogenic | -1.584 | Destabilizing | 1.0 | D | 0.865 | deleterious | None | None | None | None | N |
| I/L | 0.174 | likely_benign | 0.1314 | benign | -0.946 | Destabilizing | 0.889 | D | 0.473 | neutral | D | 0.578436562 | None | None | N |
| I/M | 0.1437 | likely_benign | 0.1249 | benign | -0.737 | Destabilizing | 0.999 | D | 0.711 | prob.delet. | D | 0.64754544 | None | None | N |
| I/N | 0.8085 | likely_pathogenic | 0.7198 | pathogenic | -1.491 | Destabilizing | 0.999 | D | 0.861 | deleterious | D | 0.650679852 | None | None | N |
| I/P | 0.883 | likely_pathogenic | 0.8144 | pathogenic | -1.262 | Destabilizing | 1.0 | D | 0.852 | deleterious | None | None | None | None | N |
| I/Q | 0.9041 | likely_pathogenic | 0.8443 | pathogenic | -1.598 | Destabilizing | 1.0 | D | 0.858 | deleterious | None | None | None | None | N |
| I/R | 0.8599 | likely_pathogenic | 0.7673 | pathogenic | -1.009 | Destabilizing | 1.0 | D | 0.866 | deleterious | None | None | None | None | N |
| I/S | 0.7952 | likely_pathogenic | 0.707 | pathogenic | -2.091 | Highly Destabilizing | 0.998 | D | 0.849 | deleterious | D | 0.649855666 | None | None | N |
| I/T | 0.5714 | likely_pathogenic | 0.4654 | ambiguous | -1.915 | Destabilizing | 0.989 | D | 0.786 | deleterious | D | 0.649382471 | None | None | N |
| I/V | 0.1066 | likely_benign | 0.1064 | benign | -1.262 | Destabilizing | 0.333 | N | 0.205 | neutral | N | 0.513077087 | None | None | N |
| I/W | 0.9324 | likely_pathogenic | 0.8829 | pathogenic | -1.431 | Destabilizing | 1.0 | D | 0.813 | deleterious | None | None | None | None | N |
| I/Y | 0.8467 | likely_pathogenic | 0.7759 | pathogenic | -1.202 | Destabilizing | 1.0 | D | 0.769 | 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.