Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1477 | 4654;4655;4656 | chr2:178777755;178777754;178777753 | chr2:179642482;179642481;179642480 |
| N2AB | 1477 | 4654;4655;4656 | chr2:178777755;178777754;178777753 | chr2:179642482;179642481;179642480 |
| N2A | 1477 | 4654;4655;4656 | chr2:178777755;178777754;178777753 | chr2:179642482;179642481;179642480 |
| N2B | 1431 | 4516;4517;4518 | chr2:178777755;178777754;178777753 | chr2:179642482;179642481;179642480 |
| Novex-1 | 1431 | 4516;4517;4518 | chr2:178777755;178777754;178777753 | chr2:179642482;179642481;179642480 |
| Novex-2 | 1431 | 4516;4517;4518 | chr2:178777755;178777754;178777753 | chr2:179642482;179642481;179642480 |
| Novex-3 | 1477 | 4654;4655;4656 | chr2:178777755;178777754;178777753 | chr2:179642482;179642481;179642480 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/H | rs532313981  |
0.197 | 1.0 | N | 0.754 | 0.527 | 0.415564226483 | gnomAD-2.1.1 | 1.99E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 1.63335E-04 | None | 0 | 0 | 0 |
| D/H | rs532313981 |
0.197 | 1.0 | N | 0.754 | 0.527 | 0.415564226483 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.07125E-04 | 0 |
| D/H | rs532313981 |
0.197 | 1.0 | N | 0.754 | 0.527 | 0.415564226483 | 1000 genomes | 1.99681E-04 | None | None | None | None | I | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 1E-03 | None |
| D/H | rs532313981 |
0.197 | 1.0 | N | 0.754 | 0.527 | 0.415564226483 | gnomAD-4.0.0 | 4.33705E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 7.68859E-05 | 0 |
| D/Y | None | None | 1.0 | D | 0.778 | 0.521 | 0.755161906893 | gnomAD-4.0.0 | 6.84128E-07 | None | None | None | None | I | None | 2.98829E-05 | 0 | None | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.9273 | likely_pathogenic | 0.9467 | pathogenic | -0.547 | Destabilizing | 1.0 | D | 0.754 | deleterious | N | 0.503108516 | None | None | I |
| D/C | 0.9938 | likely_pathogenic | 0.9959 | pathogenic | -0.177 | Destabilizing | 1.0 | D | 0.767 | deleterious | None | None | None | None | I |
| D/E | 0.8317 | likely_pathogenic | 0.8699 | pathogenic | -0.623 | Destabilizing | 1.0 | D | 0.457 | neutral | N | 0.472666886 | None | None | I |
| D/F | 0.9859 | likely_pathogenic | 0.9913 | pathogenic | -0.123 | Destabilizing | 1.0 | D | 0.787 | deleterious | None | None | None | None | I |
| D/G | 0.9459 | likely_pathogenic | 0.9623 | pathogenic | -0.902 | Destabilizing | 1.0 | D | 0.758 | deleterious | D | 0.582194354 | None | None | I |
| D/H | 0.9437 | likely_pathogenic | 0.9323 | pathogenic | -0.43 | Destabilizing | 1.0 | D | 0.754 | deleterious | N | 0.511817793 | None | None | I |
| D/I | 0.9652 | likely_pathogenic | 0.9789 | pathogenic | 0.392 | Stabilizing | 1.0 | D | 0.797 | deleterious | None | None | None | None | I |
| D/K | 0.9862 | likely_pathogenic | 0.9911 | pathogenic | -0.218 | Destabilizing | 1.0 | D | 0.789 | deleterious | None | None | None | None | I |
| D/L | 0.9547 | likely_pathogenic | 0.9706 | pathogenic | 0.392 | Stabilizing | 1.0 | D | 0.804 | deleterious | None | None | None | None | I |
| D/M | 0.9921 | likely_pathogenic | 0.9952 | pathogenic | 0.799 | Stabilizing | 1.0 | D | 0.771 | deleterious | None | None | None | None | I |
| D/N | 0.6089 | likely_pathogenic | 0.6799 | pathogenic | -0.705 | Destabilizing | 1.0 | D | 0.668 | neutral | N | 0.506703561 | None | None | I |
| D/P | 0.9849 | likely_pathogenic | 0.9888 | pathogenic | 0.104 | Stabilizing | 1.0 | D | 0.793 | deleterious | None | None | None | None | I |
| D/Q | 0.9694 | likely_pathogenic | 0.9787 | pathogenic | -0.567 | Destabilizing | 1.0 | D | 0.727 | prob.delet. | None | None | None | None | I |
| D/R | 0.9828 | likely_pathogenic | 0.9882 | pathogenic | -0.081 | Destabilizing | 1.0 | D | 0.779 | deleterious | None | None | None | None | I |
| D/S | 0.7751 | likely_pathogenic | 0.8267 | pathogenic | -0.955 | Destabilizing | 1.0 | D | 0.692 | prob.neutral | None | None | None | None | I |
| D/T | 0.9301 | likely_pathogenic | 0.9525 | pathogenic | -0.658 | Destabilizing | 1.0 | D | 0.792 | deleterious | None | None | None | None | I |
| D/V | 0.9262 | likely_pathogenic | 0.9509 | pathogenic | 0.104 | Stabilizing | 1.0 | D | 0.8 | deleterious | N | 0.511817793 | None | None | I |
| D/W | 0.9982 | likely_pathogenic | 0.9988 | pathogenic | 0.083 | Stabilizing | 1.0 | D | 0.752 | deleterious | None | None | None | None | I |
| D/Y | 0.9316 | likely_pathogenic | 0.9523 | pathogenic | 0.139 | Stabilizing | 1.0 | D | 0.778 | deleterious | D | 0.55532066 | 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.