Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 9581 | 28966;28967;28968 | chr2:178709578;178709577;178709576 | chr2:179574305;179574304;179574303 |
| N2AB | 9264 | 28015;28016;28017 | chr2:178709578;178709577;178709576 | chr2:179574305;179574304;179574303 |
| N2A | 8337 | 25234;25235;25236 | chr2:178709578;178709577;178709576 | chr2:179574305;179574304;179574303 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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/T | None | None | 0.096 | None | 0.661 | 0.264 | 0.556224665151 | gnomAD-4.0.0 | 1.61211E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.91542E-06 | 0 | 0 |
| I/V | rs371826762  |
-1.084 | None | None | 0.264 | 0.066 | None | gnomAD-2.1.1 | 1.64695E-04 | None | None | None | None | N | None | 0 | 1.13437E-04 | None | 2.13302E-03 | 1.02459E-04 | None | 0 | None | 0 | 1.09813E-04 | 5.63857E-04 |
| I/V | rs371826762 |
-1.084 | None | None | 0.264 | 0.066 | None | gnomAD-3.1.2 | 1.77342E-04 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 2.30415E-03 | 1.92234E-04 | None | 0 | 2.21519E-02 | 1.32271E-04 | 0 | 4.78011E-04 |
| I/V | rs371826762 |
-1.084 | None | None | 0.264 | 0.066 | None | gnomAD-4.0.0 | 1.79959E-04 | None | None | None | None | N | None | 1.33515E-05 | 1.33587E-04 | None | 2.50643E-03 | 8.95135E-05 | None | 0 | 6.48056E-03 | 1.18494E-04 | 3.30113E-05 | 3.3799E-04 |
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 | 0.6261 | likely_pathogenic | 0.5741 | pathogenic | -2.549 | Highly Destabilizing | 0.055 | N | 0.596 | neutral | None | None | None | None | N |
| I/C | 0.9113 | likely_pathogenic | 0.9152 | pathogenic | -2.066 | Highly Destabilizing | 0.667 | D | 0.77 | deleterious | None | None | None | None | N |
| I/D | 0.9967 | likely_pathogenic | 0.9965 | pathogenic | -2.64 | Highly Destabilizing | 0.667 | D | 0.81 | deleterious | None | None | None | None | N |
| I/E | 0.9903 | likely_pathogenic | 0.9889 | pathogenic | -2.354 | Highly Destabilizing | 0.667 | D | 0.797 | deleterious | None | None | None | None | N |
| I/F | 0.5387 | ambiguous | 0.5336 | ambiguous | -1.496 | Destabilizing | 0.175 | N | 0.662 | neutral | None | None | None | None | N |
| I/G | 0.97 | likely_pathogenic | 0.9672 | pathogenic | -3.156 | Highly Destabilizing | 0.364 | N | 0.774 | deleterious | None | None | None | None | N |
| I/H | 0.9855 | likely_pathogenic | 0.9828 | pathogenic | -2.683 | Highly Destabilizing | 0.958 | D | 0.823 | deleterious | None | None | None | None | N |
| I/K | 0.9785 | likely_pathogenic | 0.9748 | pathogenic | -1.859 | Destabilizing | 0.364 | N | 0.794 | deleterious | None | None | None | None | N |
| I/L | 0.2172 | likely_benign | 0.2125 | benign | -0.768 | Destabilizing | None | N | 0.288 | neutral | None | None | None | None | N |
| I/M | 0.227 | likely_benign | 0.2121 | benign | -0.979 | Destabilizing | 0.655 | D | 0.649 | neutral | None | None | None | None | N |
| I/N | 0.962 | likely_pathogenic | 0.9577 | pathogenic | -2.351 | Highly Destabilizing | 0.822 | D | 0.818 | deleterious | None | None | None | None | N |
| I/P | 0.9889 | likely_pathogenic | 0.9867 | pathogenic | -1.345 | Destabilizing | 0.859 | D | 0.815 | deleterious | None | None | None | None | N |
| I/Q | 0.981 | likely_pathogenic | 0.9776 | pathogenic | -2.081 | Highly Destabilizing | 0.859 | D | 0.821 | deleterious | None | None | None | None | N |
| I/R | 0.9605 | likely_pathogenic | 0.9545 | pathogenic | -1.809 | Destabilizing | 0.667 | D | 0.817 | deleterious | None | None | None | None | N |
| I/S | 0.8918 | likely_pathogenic | 0.8736 | pathogenic | -3.119 | Highly Destabilizing | 0.175 | N | 0.73 | prob.delet. | None | None | None | None | N |
| I/T | 0.6138 | likely_pathogenic | 0.5308 | ambiguous | -2.661 | Highly Destabilizing | 0.096 | N | 0.661 | neutral | None | None | None | None | N |
| I/V | 0.0597 | likely_benign | 0.058 | benign | -1.345 | Destabilizing | None | N | 0.264 | neutral | None | None | None | None | N |
| I/W | 0.9856 | likely_pathogenic | 0.9848 | pathogenic | -1.83 | Destabilizing | 0.958 | D | 0.819 | deleterious | None | None | None | None | N |
| I/Y | 0.9485 | likely_pathogenic | 0.9474 | pathogenic | -1.551 | Destabilizing | 0.667 | D | 0.768 | 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.