Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1300 | 4123;4124;4125 | chr2:178779294;178779293;178779292 | chr2:179644021;179644020;179644019 |
| N2AB | 1300 | 4123;4124;4125 | chr2:178779294;178779293;178779292 | chr2:179644021;179644020;179644019 |
| N2A | 1300 | 4123;4124;4125 | chr2:178779294;178779293;178779292 | chr2:179644021;179644020;179644019 |
| N2B | 1254 | 3985;3986;3987 | chr2:178779294;178779293;178779292 | chr2:179644021;179644020;179644019 |
| Novex-1 | 1254 | 3985;3986;3987 | chr2:178779294;178779293;178779292 | chr2:179644021;179644020;179644019 |
| Novex-2 | 1254 | 3985;3986;3987 | chr2:178779294;178779293;178779292 | chr2:179644021;179644020;179644019 |
| Novex-3 | 1300 | 4123;4124;4125 | chr2:178779294;178779293;178779292 | chr2:179644021;179644020;179644019 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/C | rs188090472  |
-1.228 | 1.0 | N | 0.764 | 0.651 | None | gnomAD-2.1.1 | 2E-05 | None | None | None | None | I | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 3.55E-05 | 0 |
| Y/C | rs188090472 |
-1.228 | 1.0 | N | 0.764 | 0.651 | None | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 5.88E-05 | 0 | 0 |
| Y/C | rs188090472 |
-1.228 | 1.0 | N | 0.764 | 0.651 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | I | None | 0 | 0 | None | None | 0 | 1E-03 | None | None | None | 0 | None |
| Y/C | rs188090472 |
-1.228 | 1.0 | N | 0.764 | 0.651 | None | gnomAD-4.0.0 | 1.79729E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.45857E-05 | 0 | 0 |
| Y/H | rs1574706508 |
None | 1.0 | N | 0.674 | 0.528 | 0.585382094262 | gnomAD-4.0.0 | 1.36849E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79896E-06 | 0 | 0 |
| Y/N | None | None | 1.0 | N | 0.805 | 0.706 | 0.819341713775 | gnomAD-4.0.0 | 6.84244E-07 | None | None | None | None | I | None | 0 | 0 | None | 3.82702E-05 | 0 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/A | 0.7741 | likely_pathogenic | 0.7787 | pathogenic | -2.209 | Highly Destabilizing | 1.0 | D | 0.731 | prob.delet. | None | None | None | None | I |
| Y/C | 0.3693 | ambiguous | 0.3297 | benign | -1.42 | Destabilizing | 1.0 | D | 0.764 | deleterious | N | 0.477044254 | None | None | I |
| Y/D | 0.8146 | likely_pathogenic | 0.8275 | pathogenic | -1.118 | Destabilizing | 1.0 | D | 0.815 | deleterious | D | 0.553840321 | None | None | I |
| Y/E | 0.8992 | likely_pathogenic | 0.9028 | pathogenic | -0.974 | Destabilizing | 1.0 | D | 0.792 | deleterious | None | None | None | None | I |
| Y/F | 0.1255 | likely_benign | 0.1299 | benign | -0.787 | Destabilizing | 0.999 | D | 0.509 | neutral | N | 0.465365153 | None | None | I |
| Y/G | 0.8148 | likely_pathogenic | 0.8229 | pathogenic | -2.566 | Highly Destabilizing | 1.0 | D | 0.783 | deleterious | None | None | None | None | I |
| Y/H | 0.4333 | ambiguous | 0.4439 | ambiguous | -1.025 | Destabilizing | 1.0 | D | 0.674 | neutral | N | 0.490300964 | None | None | I |
| Y/I | 0.6652 | likely_pathogenic | 0.6609 | pathogenic | -1.098 | Destabilizing | 1.0 | D | 0.77 | deleterious | None | None | None | None | I |
| Y/K | 0.8743 | likely_pathogenic | 0.8773 | pathogenic | -1.577 | Destabilizing | 1.0 | D | 0.793 | deleterious | None | None | None | None | I |
| Y/L | 0.6467 | likely_pathogenic | 0.6464 | pathogenic | -1.098 | Destabilizing | 0.999 | D | 0.68 | prob.neutral | None | None | None | None | I |
| Y/M | 0.7618 | likely_pathogenic | 0.7689 | pathogenic | -1.014 | Destabilizing | 1.0 | D | 0.727 | prob.delet. | None | None | None | None | I |
| Y/N | 0.5617 | ambiguous | 0.5901 | pathogenic | -2.142 | Highly Destabilizing | 1.0 | D | 0.805 | deleterious | N | 0.505255696 | None | None | I |
| Y/P | 0.9917 | likely_pathogenic | 0.9929 | pathogenic | -1.468 | Destabilizing | 1.0 | D | 0.803 | deleterious | None | None | None | None | I |
| Y/Q | 0.7544 | likely_pathogenic | 0.7633 | pathogenic | -1.888 | Destabilizing | 1.0 | D | 0.791 | deleterious | None | None | None | None | I |
| Y/R | 0.7446 | likely_pathogenic | 0.7462 | pathogenic | -1.375 | Destabilizing | 1.0 | D | 0.804 | deleterious | None | None | None | None | I |
| Y/S | 0.5356 | ambiguous | 0.5387 | ambiguous | -2.665 | Highly Destabilizing | 1.0 | D | 0.789 | deleterious | N | 0.482954944 | None | None | I |
| Y/T | 0.7107 | likely_pathogenic | 0.7242 | pathogenic | -2.407 | Highly Destabilizing | 1.0 | D | 0.792 | deleterious | None | None | None | None | I |
| Y/V | 0.5519 | ambiguous | 0.5532 | ambiguous | -1.468 | Destabilizing | 1.0 | D | 0.721 | prob.delet. | None | None | None | None | I |
| Y/W | 0.6441 | likely_pathogenic | 0.6542 | pathogenic | -0.306 | Destabilizing | 1.0 | D | 0.659 | neutral | None | None | None | None | I |
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.