Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30400 | 91423;91424;91425 | chr2:178551702;178551701;178551700 | chr2:179416429;179416428;179416427 |
| N2AB | 28759 | 86500;86501;86502 | chr2:178551702;178551701;178551700 | chr2:179416429;179416428;179416427 |
| N2A | 27832 | 83719;83720;83721 | chr2:178551702;178551701;178551700 | chr2:179416429;179416428;179416427 |
| N2B | 21335 | 64228;64229;64230 | chr2:178551702;178551701;178551700 | chr2:179416429;179416428;179416427 |
| Novex-1 | 21460 | 64603;64604;64605 | chr2:178551702;178551701;178551700 | chr2:179416429;179416428;179416427 |
| Novex-2 | 21527 | 64804;64805;64806 | chr2:178551702;178551701;178551700 | chr2:179416429;179416428;179416427 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/C | rs376494747  |
-1.957 | 0.001 | N | 0.643 | 0.293 | None | gnomAD-2.1.1 | 8.05E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 8.89E-06 | 0 |
| Y/C | rs376494747 |
-1.957 | 0.001 | N | 0.643 | 0.293 | None | gnomAD-4.0.0 | 1.36887E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99713E-07 | 1.16015E-05 | 0 |
| Y/F | rs376494747 |
-1.663 | None | N | 0.307 | 0.063 | 0.170165803431 | gnomAD-2.1.1 | 7.25E-05 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 1.49432E-03 | 0 | None | 0 | None | 0 | 1.78E-05 | 0 |
| Y/F | rs376494747 |
-1.663 | None | N | 0.307 | 0.063 | 0.170165803431 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 2.88018E-04 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| Y/F | rs376494747 |
-1.663 | None | N | 0.307 | 0.063 | 0.170165803431 | gnomAD-4.0.0 | 4.52495E-05 | None | None | None | None | N | None | 0 | 1.66795E-05 | None | 1.14919E-03 | 0 | None | 0 | 1.64528E-04 | 1.94998E-05 | 2.19698E-05 | 1.92184E-04 |
| Y/H | rs753682966 |
None | 0.484 | N | 0.694 | 0.308 | 0.353974658523 | gnomAD-4.0.0 | 6.84418E-07 | None | None | None | None | N | None | 2.99079E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| Y/N | rs753682966 |
-3.142 | 0.741 | N | 0.697 | 0.383 | 0.672318618897 | gnomAD-2.1.1 | 8.05E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.78E-05 | 0 |
| Y/N | rs753682966 |
-3.142 | 0.741 | N | 0.697 | 0.383 | 0.672318618897 | gnomAD-4.0.0 | 2.05325E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.69906E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/A | 0.3601 | ambiguous | 0.4334 | ambiguous | -3.524 | Highly Destabilizing | 0.081 | N | 0.703 | prob.neutral | None | None | None | None | N |
| Y/C | 0.0833 | likely_benign | 0.1103 | benign | -1.885 | Destabilizing | 0.001 | N | 0.643 | neutral | N | 0.489582834 | None | None | N |
| Y/D | 0.6113 | likely_pathogenic | 0.705 | pathogenic | -3.42 | Highly Destabilizing | 0.741 | D | 0.715 | prob.delet. | N | 0.494486242 | None | None | N |
| Y/E | 0.7562 | likely_pathogenic | 0.8236 | pathogenic | -3.285 | Highly Destabilizing | 0.555 | D | 0.691 | prob.neutral | None | None | None | None | N |
| Y/F | 0.0585 | likely_benign | 0.0587 | benign | -1.447 | Destabilizing | None | N | 0.307 | neutral | N | 0.464820462 | None | None | N |
| Y/G | 0.4432 | ambiguous | 0.5344 | ambiguous | -3.866 | Highly Destabilizing | 0.38 | N | 0.698 | prob.neutral | None | None | None | None | N |
| Y/H | 0.164 | likely_benign | 0.1917 | benign | -2.21 | Highly Destabilizing | 0.484 | N | 0.694 | prob.neutral | N | 0.471609047 | None | None | N |
| Y/I | 0.2297 | likely_benign | 0.2842 | benign | -2.388 | Highly Destabilizing | 0.081 | N | 0.669 | neutral | None | None | None | None | N |
| Y/K | 0.6229 | likely_pathogenic | 0.672 | pathogenic | -2.245 | Highly Destabilizing | 0.555 | D | 0.686 | prob.neutral | None | None | None | None | N |
| Y/L | 0.3063 | likely_benign | 0.3659 | ambiguous | -2.388 | Highly Destabilizing | 0.001 | N | 0.463 | neutral | None | None | None | None | N |
| Y/M | 0.3469 | ambiguous | 0.3956 | ambiguous | -1.944 | Destabilizing | 0.38 | N | 0.676 | prob.neutral | None | None | None | None | N |
| Y/N | 0.244 | likely_benign | 0.308 | benign | -2.74 | Highly Destabilizing | 0.741 | D | 0.697 | prob.neutral | N | 0.476381987 | None | None | N |
| Y/P | 0.9802 | likely_pathogenic | 0.9882 | pathogenic | -2.779 | Highly Destabilizing | 0.791 | D | 0.727 | prob.delet. | None | None | None | None | N |
| Y/Q | 0.4293 | ambiguous | 0.5159 | ambiguous | -2.674 | Highly Destabilizing | 0.791 | D | 0.687 | prob.neutral | None | None | None | None | N |
| Y/R | 0.3901 | ambiguous | 0.4672 | ambiguous | -1.651 | Destabilizing | 0.555 | D | 0.697 | prob.neutral | None | None | None | None | N |
| Y/S | 0.1514 | likely_benign | 0.1814 | benign | -3.123 | Highly Destabilizing | 0.317 | N | 0.684 | prob.neutral | N | 0.430265171 | None | None | N |
| Y/T | 0.2827 | likely_benign | 0.3379 | benign | -2.897 | Highly Destabilizing | 0.38 | N | 0.683 | prob.neutral | None | None | None | None | N |
| Y/V | 0.2142 | likely_benign | 0.2635 | benign | -2.779 | Highly Destabilizing | 0.081 | N | 0.689 | prob.neutral | None | None | None | None | N |
| Y/W | 0.3285 | likely_benign | 0.3562 | ambiguous | -0.831 | Destabilizing | 0.824 | D | 0.689 | prob.neutral | 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.