Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 7471 | 22636;22637;22638 | chr2:178722376;178722375;178722374 | chr2:179587103;179587102;179587101 |
| N2AB | 7154 | 21685;21686;21687 | chr2:178722376;178722375;178722374 | chr2:179587103;179587102;179587101 |
| N2A | 6227 | 18904;18905;18906 | chr2:178722376;178722375;178722374 | chr2:179587103;179587102;179587101 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/G | rs760724710  |
0.026 | 0.955 | N | 0.516 | 0.416 | 0.324436698001 | gnomAD-2.1.1 | 1.61E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 3.58E-05 | 0 |
| D/G | rs760724710 |
0.026 | 0.955 | N | 0.516 | 0.416 | 0.324436698001 | gnomAD-4.0.0 | 1.59212E-05 | None | None | None | None | I | None | 0 | 2.2877E-05 | None | 0 | 0 | None | 0 | 0 | 2.57381E-05 | 0 | 0 |
| D/N | rs1174976870 |
0.056 | 0.117 | N | 0.251 | 0.197 | 0.230578612272 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 5.59E-05 | None | 0 | None | 0 | 0 | 0 |
| D/N | rs1174976870 |
0.056 | 0.117 | N | 0.251 | 0.197 | 0.230578612272 | gnomAD-4.0.0 | 1.59219E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 2.77546E-05 | 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 | 0.2723 | likely_benign | 0.2666 | benign | -0.065 | Destabilizing | 0.993 | D | 0.48 | neutral | N | 0.485376842 | None | None | I |
| D/C | 0.808 | likely_pathogenic | 0.8103 | pathogenic | -0.174 | Destabilizing | 1.0 | D | 0.695 | prob.neutral | None | None | None | None | I |
| D/E | 0.2342 | likely_benign | 0.2695 | benign | -0.334 | Destabilizing | 0.977 | D | 0.405 | neutral | N | 0.480395708 | None | None | I |
| D/F | 0.7976 | likely_pathogenic | 0.7868 | pathogenic | -0.038 | Destabilizing | 1.0 | D | 0.649 | neutral | None | None | None | None | I |
| D/G | 0.1644 | likely_benign | 0.174 | benign | -0.213 | Destabilizing | 0.955 | D | 0.516 | neutral | N | 0.49434644 | None | None | I |
| D/H | 0.3688 | ambiguous | 0.3944 | ambiguous | 0.483 | Stabilizing | 0.999 | D | 0.621 | neutral | D | 0.522823908 | None | None | I |
| D/I | 0.7875 | likely_pathogenic | 0.7739 | pathogenic | 0.264 | Stabilizing | 0.999 | D | 0.643 | neutral | None | None | None | None | I |
| D/K | 0.5319 | ambiguous | 0.5432 | ambiguous | 0.4 | Stabilizing | 0.995 | D | 0.545 | neutral | None | None | None | None | I |
| D/L | 0.6491 | likely_pathogenic | 0.6281 | pathogenic | 0.264 | Stabilizing | 0.998 | D | 0.611 | neutral | None | None | None | None | I |
| D/M | 0.8372 | likely_pathogenic | 0.8316 | pathogenic | 0.086 | Stabilizing | 1.0 | D | 0.671 | neutral | None | None | None | None | I |
| D/N | 0.1063 | likely_benign | 0.1169 | benign | 0.038 | Stabilizing | 0.117 | N | 0.251 | neutral | N | 0.487113824 | None | None | I |
| D/P | 0.8798 | likely_pathogenic | 0.8665 | pathogenic | 0.175 | Stabilizing | 0.999 | D | 0.589 | neutral | None | None | None | None | I |
| D/Q | 0.4363 | ambiguous | 0.4686 | ambiguous | 0.061 | Stabilizing | 0.998 | D | 0.6 | neutral | None | None | None | None | I |
| D/R | 0.4986 | ambiguous | 0.5072 | ambiguous | 0.663 | Stabilizing | 0.995 | D | 0.569 | neutral | None | None | None | None | I |
| D/S | 0.1737 | likely_benign | 0.1889 | benign | -0.032 | Destabilizing | 0.966 | D | 0.51 | neutral | None | None | None | None | I |
| D/T | 0.5183 | ambiguous | 0.5113 | ambiguous | 0.09 | Stabilizing | 0.995 | D | 0.523 | neutral | None | None | None | None | I |
| D/V | 0.5801 | likely_pathogenic | 0.5466 | ambiguous | 0.175 | Stabilizing | 0.997 | D | 0.616 | neutral | N | 0.518675744 | None | None | I |
| D/W | 0.9338 | likely_pathogenic | 0.9243 | pathogenic | 0.048 | Stabilizing | 1.0 | D | 0.709 | prob.delet. | None | None | None | None | I |
| D/Y | 0.3667 | ambiguous | 0.3472 | ambiguous | 0.194 | Stabilizing | 1.0 | D | 0.649 | neutral | N | 0.505193071 | 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.