Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18962 | 57109;57110;57111 | chr2:178598826;178598825;178598824 | chr2:179463553;179463552;179463551 |
| N2AB | 17321 | 52186;52187;52188 | chr2:178598826;178598825;178598824 | chr2:179463553;179463552;179463551 |
| N2A | 16394 | 49405;49406;49407 | chr2:178598826;178598825;178598824 | chr2:179463553;179463552;179463551 |
| N2B | 9897 | 29914;29915;29916 | chr2:178598826;178598825;178598824 | chr2:179463553;179463552;179463551 |
| Novex-1 | 10022 | 30289;30290;30291 | chr2:178598826;178598825;178598824 | chr2:179463553;179463552;179463551 |
| Novex-2 | 10089 | 30490;30491;30492 | chr2:178598826;178598825;178598824 | chr2:179463553;179463552;179463551 |
| 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/Q | rs141399146  |
-0.974 | 0.998 | N | 0.511 | 0.471 | None | gnomAD-2.1.1 | 2.01E-05 | None | None | None | None | N | None | 1.942E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.78E-05 | 0 |
| R/Q | rs141399146 |
-0.974 | 0.998 | N | 0.511 | 0.471 | None | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 7.24E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/Q | rs141399146 |
-0.974 | 0.998 | N | 0.511 | 0.471 | None | 1000 genomes | 3.99361E-04 | None | None | None | None | N | None | 1.5E-03 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| R/Q | rs141399146 |
-0.974 | 0.998 | N | 0.511 | 0.471 | None | gnomAD-4.0.0 | 2.10745E-05 | None | None | None | None | N | None | 6.66791E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 2.03475E-05 | 2.1964E-05 | 4.80323E-05 |
| R/W | rs556286196 |
-0.82 | 1.0 | D | 0.67 | 0.526 | 0.685903383558 | gnomAD-2.1.1 | 8.06E-06 | None | None | None | None | N | None | 0 | 0 | None | 9.97E-05 | 0 | None | 0 | None | 0 | 8.91E-06 | 0 |
| R/W | rs556286196 |
-0.82 | 1.0 | D | 0.67 | 0.526 | 0.685903383558 | gnomAD-3.1.2 | 3.95E-05 | None | None | None | None | N | None | 9.65E-05 | 0 | 0 | 0 | 1.94326E-04 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/W | rs556286196 |
-0.82 | 1.0 | D | 0.67 | 0.526 | 0.685903383558 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 1E-03 | 0 | None | None | None | 0 | None |
| R/W | rs556286196 |
-0.82 | 1.0 | D | 0.67 | 0.526 | 0.685903383558 | gnomAD-4.0.0 | 1.23969E-05 | None | None | None | None | N | None | 8.00064E-05 | 0 | None | 3.37929E-05 | 1.11697E-04 | None | 0 | 0 | 5.08692E-06 | 0 | 3.20184E-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 | 0.9945 | likely_pathogenic | 0.9902 | pathogenic | -2.11 | Highly Destabilizing | 0.953 | D | 0.565 | neutral | None | None | None | None | N |
| R/C | 0.7605 | likely_pathogenic | 0.7546 | pathogenic | -1.866 | Destabilizing | 0.999 | D | 0.73 | prob.delet. | None | None | None | None | N |
| R/D | 0.9994 | likely_pathogenic | 0.9989 | pathogenic | -1.099 | Destabilizing | 0.993 | D | 0.579 | neutral | None | None | None | None | N |
| R/E | 0.9892 | likely_pathogenic | 0.9801 | pathogenic | -0.869 | Destabilizing | 0.953 | D | 0.546 | neutral | None | None | None | None | N |
| R/F | 0.9945 | likely_pathogenic | 0.9927 | pathogenic | -1.216 | Destabilizing | 0.999 | D | 0.737 | prob.delet. | None | None | None | None | N |
| R/G | 0.9955 | likely_pathogenic | 0.9912 | pathogenic | -2.453 | Highly Destabilizing | 0.975 | D | 0.563 | neutral | D | 0.549046632 | None | None | N |
| R/H | 0.4847 | ambiguous | 0.484 | ambiguous | -2.139 | Highly Destabilizing | 0.998 | D | 0.558 | neutral | None | None | None | None | N |
| R/I | 0.9816 | likely_pathogenic | 0.9726 | pathogenic | -1.099 | Destabilizing | 0.993 | D | 0.723 | prob.delet. | None | None | None | None | N |
| R/K | 0.5817 | likely_pathogenic | 0.6321 | pathogenic | -1.181 | Destabilizing | 0.893 | D | 0.61 | neutral | None | None | None | None | N |
| R/L | 0.9662 | likely_pathogenic | 0.9503 | pathogenic | -1.099 | Destabilizing | 0.975 | D | 0.56 | neutral | N | 0.508483256 | None | None | N |
| R/M | 0.985 | likely_pathogenic | 0.9809 | pathogenic | -1.6 | Destabilizing | 0.999 | D | 0.6 | neutral | None | None | None | None | N |
| R/N | 0.9964 | likely_pathogenic | 0.9942 | pathogenic | -1.348 | Destabilizing | 0.993 | D | 0.503 | neutral | None | None | None | None | N |
| R/P | 0.9997 | likely_pathogenic | 0.9995 | pathogenic | -1.428 | Destabilizing | 0.109 | N | 0.58 | neutral | D | 0.549553611 | None | None | N |
| R/Q | 0.6429 | likely_pathogenic | 0.5915 | pathogenic | -1.171 | Destabilizing | 0.998 | D | 0.511 | neutral | N | 0.488591348 | None | None | N |
| R/S | 0.9957 | likely_pathogenic | 0.9922 | pathogenic | -2.224 | Highly Destabilizing | 0.953 | D | 0.529 | neutral | None | None | None | None | N |
| R/T | 0.9931 | likely_pathogenic | 0.9877 | pathogenic | -1.78 | Destabilizing | 0.953 | D | 0.524 | neutral | None | None | None | None | N |
| R/V | 0.9828 | likely_pathogenic | 0.9749 | pathogenic | -1.428 | Destabilizing | 0.993 | D | 0.69 | prob.neutral | None | None | None | None | N |
| R/W | 0.915 | likely_pathogenic | 0.8956 | pathogenic | -0.723 | Destabilizing | 1.0 | D | 0.67 | neutral | D | 0.531195867 | None | None | N |
| R/Y | 0.9812 | likely_pathogenic | 0.9785 | pathogenic | -0.629 | Destabilizing | 0.998 | D | 0.688 | 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.