Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 33013 | 99262;99263;99264 | chr2:178538792;178538791;178538790 | chr2:179403519;179403518;179403517 |
| N2AB | 31372 | 94339;94340;94341 | chr2:178538792;178538791;178538790 | chr2:179403519;179403518;179403517 |
| N2A | 30445 | 91558;91559;91560 | chr2:178538792;178538791;178538790 | chr2:179403519;179403518;179403517 |
| N2B | 23948 | 72067;72068;72069 | chr2:178538792;178538791;178538790 | chr2:179403519;179403518;179403517 |
| Novex-1 | 24073 | 72442;72443;72444 | chr2:178538792;178538791;178538790 | chr2:179403519;179403518;179403517 |
| Novex-2 | 24140 | 72643;72644;72645 | chr2:178538792;178538791;178538790 | chr2:179403519;179403518;179403517 |
| 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 | rs749756106  |
-1.107 | 1.0 | N | 0.731 | 0.529 | 0.303781844768 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.91E-06 | 0 |
| D/H | rs1342105550 |
-0.942 | 1.0 | N | 0.743 | 0.416 | 0.321108458156 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 4.67E-05 | 0 | 0 |
| D/H | rs1342105550 |
-0.942 | 1.0 | N | 0.743 | 0.416 | 0.321108458156 | gnomAD-4.0.0 | 1.59437E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 1.88509E-05 | 0 | 0 | 0 | 0 |
| D/N | rs1342105550 |
None | 1.0 | N | 0.578 | 0.294 | 0.230578612272 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| D/N | rs1342105550 |
None | 1.0 | N | 0.578 | 0.294 | 0.230578612272 | gnomAD-4.0.0 | 6.57203E-06 | None | None | None | None | I | None | 2.41301E-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 | 0.6257 | likely_pathogenic | 0.7277 | pathogenic | -0.515 | Destabilizing | 1.0 | D | 0.793 | deleterious | N | 0.490753714 | None | None | I |
| D/C | 0.9308 | likely_pathogenic | 0.9597 | pathogenic | 0.196 | Stabilizing | 1.0 | D | 0.743 | deleterious | None | None | None | None | I |
| D/E | 0.381 | ambiguous | 0.4424 | ambiguous | -0.333 | Destabilizing | 1.0 | D | 0.443 | neutral | N | 0.520193742 | None | None | I |
| D/F | 0.891 | likely_pathogenic | 0.9296 | pathogenic | -0.706 | Destabilizing | 1.0 | D | 0.791 | deleterious | None | None | None | None | I |
| D/G | 0.4637 | ambiguous | 0.579 | pathogenic | -0.694 | Destabilizing | 1.0 | D | 0.731 | prob.delet. | N | 0.480371687 | None | None | I |
| D/H | 0.7445 | likely_pathogenic | 0.8269 | pathogenic | -0.813 | Destabilizing | 1.0 | D | 0.743 | deleterious | N | 0.486145358 | None | None | I |
| D/I | 0.87 | likely_pathogenic | 0.9147 | pathogenic | -0.089 | Destabilizing | 1.0 | D | 0.782 | deleterious | None | None | None | None | I |
| D/K | 0.8837 | likely_pathogenic | 0.9259 | pathogenic | 0.321 | Stabilizing | 1.0 | D | 0.783 | deleterious | None | None | None | None | I |
| D/L | 0.8381 | likely_pathogenic | 0.8975 | pathogenic | -0.089 | Destabilizing | 1.0 | D | 0.779 | deleterious | None | None | None | None | I |
| D/M | 0.924 | likely_pathogenic | 0.9538 | pathogenic | 0.352 | Stabilizing | 1.0 | D | 0.738 | prob.delet. | None | None | None | None | I |
| D/N | 0.1839 | likely_benign | 0.2444 | benign | 0.096 | Stabilizing | 1.0 | D | 0.578 | neutral | N | 0.465857825 | None | None | I |
| D/P | 0.9919 | likely_pathogenic | 0.9954 | pathogenic | -0.211 | Destabilizing | 1.0 | D | 0.777 | deleterious | None | None | None | None | I |
| D/Q | 0.7954 | likely_pathogenic | 0.8632 | pathogenic | 0.094 | Stabilizing | 1.0 | D | 0.735 | prob.delet. | None | None | None | None | I |
| D/R | 0.8989 | likely_pathogenic | 0.9392 | pathogenic | 0.256 | Stabilizing | 1.0 | D | 0.799 | deleterious | None | None | None | None | I |
| D/S | 0.3861 | ambiguous | 0.4781 | ambiguous | -0.019 | Destabilizing | 1.0 | D | 0.675 | neutral | None | None | None | None | I |
| D/T | 0.5856 | likely_pathogenic | 0.6528 | pathogenic | 0.125 | Stabilizing | 1.0 | D | 0.777 | deleterious | None | None | None | None | I |
| D/V | 0.7076 | likely_pathogenic | 0.7899 | pathogenic | -0.211 | Destabilizing | 1.0 | D | 0.777 | deleterious | N | 0.513884398 | None | None | I |
| D/W | 0.9815 | likely_pathogenic | 0.99 | pathogenic | -0.609 | Destabilizing | 1.0 | D | 0.743 | deleterious | None | None | None | None | I |
| D/Y | 0.514 | ambiguous | 0.6525 | pathogenic | -0.479 | Destabilizing | 1.0 | D | 0.781 | deleterious | N | 0.508857969 | 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.