Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31936 | 96031;96032;96033 | chr2:178544423;178544422;178544421 | chr2:179409150;179409149;179409148 |
| N2AB | 30295 | 91108;91109;91110 | chr2:178544423;178544422;178544421 | chr2:179409150;179409149;179409148 |
| N2A | 29368 | 88327;88328;88329 | chr2:178544423;178544422;178544421 | chr2:179409150;179409149;179409148 |
| N2B | 22871 | 68836;68837;68838 | chr2:178544423;178544422;178544421 | chr2:179409150;179409149;179409148 |
| Novex-1 | 22996 | 69211;69212;69213 | chr2:178544423;178544422;178544421 | chr2:179409150;179409149;179409148 |
| Novex-2 | 23063 | 69412;69413;69414 | chr2:178544423;178544422;178544421 | chr2:179409150;179409149;179409148 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/E | rs1696070748  |
None | 1.0 | N | 0.459 | 0.362 | 0.254244900254 | gnomAD-4.0.0 | 6.36576E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.14356E-05 | 0 | 0 |
| D/N | rs267599025 |
-0.911 | 1.0 | N | 0.707 | 0.412 | 0.321951552304 | gnomAD-2.1.1 | 2.5E-05 | None | None | None | None | I | None | 4.13E-05 | 1.13173E-04 | None | 0 | 0 | None | 0 | None | 0 | 1.56E-05 | 0 |
| D/N | rs267599025 |
-0.911 | 1.0 | N | 0.707 | 0.412 | 0.321951552304 | gnomAD-3.1.2 | 3.94E-05 | None | None | None | None | I | None | 9.65E-05 | 6.54E-05 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| D/N | rs267599025 |
-0.911 | 1.0 | N | 0.707 | 0.412 | 0.321951552304 | gnomAD-4.0.0 | 1.67326E-05 | None | None | None | None | I | None | 5.33931E-05 | 6.66689E-05 | None | 0 | 0 | None | 0 | 1.64474E-04 | 1.35628E-05 | 1.09798E-05 | 1.60113E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.6634 | likely_pathogenic | 0.6625 | pathogenic | -0.567 | Destabilizing | 1.0 | D | 0.74 | deleterious | N | 0.484664101 | None | None | I |
| D/C | 0.8877 | likely_pathogenic | 0.9036 | pathogenic | -0.288 | Destabilizing | 1.0 | D | 0.687 | prob.neutral | None | None | None | None | I |
| D/E | 0.6629 | likely_pathogenic | 0.6899 | pathogenic | -0.749 | Destabilizing | 1.0 | D | 0.459 | neutral | N | 0.482004301 | None | None | I |
| D/F | 0.9358 | likely_pathogenic | 0.943 | pathogenic | -0.385 | Destabilizing | 1.0 | D | 0.689 | prob.neutral | None | None | None | None | I |
| D/G | 0.6113 | likely_pathogenic | 0.606 | pathogenic | -0.929 | Destabilizing | 1.0 | D | 0.708 | prob.delet. | N | 0.511695579 | None | None | I |
| D/H | 0.7607 | likely_pathogenic | 0.7621 | pathogenic | -0.893 | Destabilizing | 1.0 | D | 0.679 | prob.neutral | N | 0.497603795 | None | None | I |
| D/I | 0.8871 | likely_pathogenic | 0.8902 | pathogenic | 0.391 | Stabilizing | 1.0 | D | 0.715 | prob.delet. | None | None | None | None | I |
| D/K | 0.8928 | likely_pathogenic | 0.9048 | pathogenic | -0.625 | Destabilizing | 1.0 | D | 0.757 | deleterious | None | None | None | None | I |
| D/L | 0.8706 | likely_pathogenic | 0.8834 | pathogenic | 0.391 | Stabilizing | 1.0 | D | 0.727 | prob.delet. | None | None | None | None | I |
| D/M | 0.952 | likely_pathogenic | 0.9563 | pathogenic | 0.931 | Stabilizing | 1.0 | D | 0.679 | prob.neutral | None | None | None | None | I |
| D/N | 0.1971 | likely_benign | 0.1761 | benign | -0.974 | Destabilizing | 1.0 | D | 0.707 | prob.neutral | N | 0.512267692 | None | None | I |
| D/P | 0.9325 | likely_pathogenic | 0.9476 | pathogenic | 0.097 | Stabilizing | 1.0 | D | 0.755 | deleterious | None | None | None | None | I |
| D/Q | 0.8612 | likely_pathogenic | 0.8733 | pathogenic | -0.795 | Destabilizing | 1.0 | D | 0.751 | deleterious | None | None | None | None | I |
| D/R | 0.8774 | likely_pathogenic | 0.8861 | pathogenic | -0.61 | Destabilizing | 1.0 | D | 0.743 | deleterious | None | None | None | None | I |
| D/S | 0.3238 | likely_benign | 0.3007 | benign | -1.277 | Destabilizing | 1.0 | D | 0.719 | prob.delet. | None | None | None | None | I |
| D/T | 0.6236 | likely_pathogenic | 0.629 | pathogenic | -0.974 | Destabilizing | 1.0 | D | 0.763 | deleterious | None | None | None | None | I |
| D/V | 0.768 | likely_pathogenic | 0.7697 | pathogenic | 0.097 | Stabilizing | 1.0 | D | 0.731 | prob.delet. | N | 0.50680728 | None | None | I |
| D/W | 0.9851 | likely_pathogenic | 0.9872 | pathogenic | -0.327 | Destabilizing | 1.0 | D | 0.678 | prob.neutral | None | None | None | None | I |
| D/Y | 0.6738 | likely_pathogenic | 0.6962 | pathogenic | -0.188 | Destabilizing | 1.0 | D | 0.67 | neutral | D | 0.534572774 | 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.