Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20908 | 62947;62948;62949 | chr2:178589003;178589002;178589001 | chr2:179453730;179453729;179453728 |
| N2AB | 19267 | 58024;58025;58026 | chr2:178589003;178589002;178589001 | chr2:179453730;179453729;179453728 |
| N2A | 18340 | 55243;55244;55245 | chr2:178589003;178589002;178589001 | chr2:179453730;179453729;179453728 |
| N2B | 11843 | 35752;35753;35754 | chr2:178589003;178589002;178589001 | chr2:179453730;179453729;179453728 |
| Novex-1 | 11968 | 36127;36128;36129 | chr2:178589003;178589002;178589001 | chr2:179453730;179453729;179453728 |
| Novex-2 | 12035 | 36328;36329;36330 | chr2:178589003;178589002;178589001 | chr2:179453730;179453729;179453728 |
| 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/P | rs377203669  |
0.278 | 1.0 | N | 0.65 | 0.435 | 0.51721326083 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | I | None | 1.14811E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| R/P | rs377203669 |
0.278 | 1.0 | N | 0.65 | 0.435 | 0.51721326083 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/P | rs377203669 |
0.278 | 1.0 | N | 0.65 | 0.435 | 0.51721326083 | gnomAD-4.0.0 | 6.57834E-06 | None | None | None | None | I | None | 2.41488E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/Q | rs377203669 |
0.081 | 1.0 | N | 0.649 | 0.434 | None | gnomAD-2.1.1 | 8.14E-05 | None | None | None | None | I | None | 6.49E-05 | 0 | None | 0 | 7.97721E-04 | None | 9.83E-05 | None | 0 | 1.8E-05 | 0 |
| R/Q | rs377203669 |
0.081 | 1.0 | N | 0.649 | 0.434 | None | gnomAD-3.1.2 | 5.92E-05 | None | None | None | None | I | None | 7.24E-05 | 0 | 0 | 0 | 7.77303E-04 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| R/Q | rs377203669 |
0.081 | 1.0 | N | 0.649 | 0.434 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | I | None | 0 | 0 | None | None | 1E-03 | 0 | None | None | None | 0 | None |
| R/Q | rs377203669 |
0.081 | 1.0 | N | 0.649 | 0.434 | None | gnomAD-4.0.0 | 3.66159E-05 | None | None | None | None | I | None | 5.33433E-05 | 5.01253E-05 | None | 0 | 4.0404E-04 | None | 1.59424E-05 | 0 | 2.20481E-05 | 4.39425E-05 | 4.80769E-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 | 0.9686 | likely_pathogenic | 0.9852 | pathogenic | -0.035 | Destabilizing | 0.999 | D | 0.469 | neutral | None | None | None | None | I |
| R/C | 0.853 | likely_pathogenic | 0.9348 | pathogenic | -0.226 | Destabilizing | 1.0 | D | 0.738 | prob.delet. | None | None | None | None | I |
| R/D | 0.9801 | likely_pathogenic | 0.9903 | pathogenic | -0.074 | Destabilizing | 1.0 | D | 0.646 | neutral | None | None | None | None | I |
| R/E | 0.9396 | likely_pathogenic | 0.9713 | pathogenic | -0.007 | Destabilizing | 0.999 | D | 0.515 | neutral | None | None | None | None | I |
| R/F | 0.9787 | likely_pathogenic | 0.9904 | pathogenic | -0.249 | Destabilizing | 1.0 | D | 0.727 | prob.delet. | None | None | None | None | I |
| R/G | 0.9111 | likely_pathogenic | 0.9557 | pathogenic | -0.234 | Destabilizing | 1.0 | D | 0.545 | neutral | N | 0.502719915 | None | None | I |
| R/H | 0.5638 | ambiguous | 0.7667 | pathogenic | -0.693 | Destabilizing | 1.0 | D | 0.687 | prob.neutral | None | None | None | None | I |
| R/I | 0.9549 | likely_pathogenic | 0.9776 | pathogenic | 0.453 | Stabilizing | 1.0 | D | 0.725 | prob.delet. | None | None | None | None | I |
| R/K | 0.5585 | ambiguous | 0.7119 | pathogenic | -0.13 | Destabilizing | 0.998 | D | 0.408 | neutral | None | None | None | None | I |
| R/L | 0.8794 | likely_pathogenic | 0.9392 | pathogenic | 0.453 | Stabilizing | 1.0 | D | 0.545 | neutral | D | 0.523463334 | None | None | I |
| R/M | 0.9495 | likely_pathogenic | 0.979 | pathogenic | 0.015 | Stabilizing | 1.0 | D | 0.672 | neutral | None | None | None | None | I |
| R/N | 0.9669 | likely_pathogenic | 0.9837 | pathogenic | 0.077 | Stabilizing | 1.0 | D | 0.651 | neutral | None | None | None | None | I |
| R/P | 0.9821 | likely_pathogenic | 0.9883 | pathogenic | 0.311 | Stabilizing | 1.0 | D | 0.65 | neutral | N | 0.474495883 | None | None | I |
| R/Q | 0.6539 | likely_pathogenic | 0.8256 | pathogenic | -0.017 | Destabilizing | 1.0 | D | 0.649 | neutral | N | 0.517998799 | None | None | I |
| R/S | 0.9781 | likely_pathogenic | 0.9896 | pathogenic | -0.288 | Destabilizing | 1.0 | D | 0.604 | neutral | None | None | None | None | I |
| R/T | 0.9568 | likely_pathogenic | 0.9792 | pathogenic | -0.085 | Destabilizing | 1.0 | D | 0.607 | neutral | None | None | None | None | I |
| R/V | 0.9626 | likely_pathogenic | 0.9823 | pathogenic | 0.311 | Stabilizing | 1.0 | D | 0.689 | prob.neutral | None | None | None | None | I |
| R/W | 0.7683 | likely_pathogenic | 0.877 | pathogenic | -0.292 | Destabilizing | 1.0 | D | 0.752 | deleterious | None | None | None | None | I |
| R/Y | 0.9213 | likely_pathogenic | 0.9658 | pathogenic | 0.117 | Stabilizing | 1.0 | D | 0.684 | prob.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.