Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31799 | 95620;95621;95622 | chr2:178545841;178545840;178545839 | chr2:179410568;179410567;179410566 |
| N2AB | 30158 | 90697;90698;90699 | chr2:178545841;178545840;178545839 | chr2:179410568;179410567;179410566 |
| N2A | 29231 | 87916;87917;87918 | chr2:178545841;178545840;178545839 | chr2:179410568;179410567;179410566 |
| N2B | 22734 | 68425;68426;68427 | chr2:178545841;178545840;178545839 | chr2:179410568;179410567;179410566 |
| Novex-1 | 22859 | 68800;68801;68802 | chr2:178545841;178545840;178545839 | chr2:179410568;179410567;179410566 |
| Novex-2 | 22926 | 69001;69002;69003 | chr2:178545841;178545840;178545839 | chr2:179410568;179410567;179410566 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/T | rs1696841409  |
None | 0.181 | N | 0.586 | 0.282 | 0.613098244845 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 6.33473E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | rs370916420 |
-1.286 | None | N | 0.144 | 0.06 | None | gnomAD-2.1.1 | 6.44E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 1.33585E-04 | 0 |
| I/V | rs370916420 |
-1.286 | None | N | 0.144 | 0.06 | None | gnomAD-3.1.2 | 4.6E-05 | None | None | None | None | N | None | 0 | 6.54E-05 | 0 | 0 | 0 | None | 0 | 3.16456E-03 | 7.35E-05 | 0 | 0 |
| I/V | rs370916420 |
-1.286 | None | N | 0.144 | 0.06 | None | gnomAD-4.0.0 | 6.01123E-05 | None | None | None | None | N | None | 0 | 1.66617E-05 | None | 0 | 0 | None | 0 | 1.65071E-04 | 7.46002E-05 | 1.09813E-05 | 9.60553E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.214 | likely_benign | 0.1921 | benign | -1.905 | Destabilizing | 0.057 | N | 0.491 | neutral | None | None | None | None | N |
| I/C | 0.5811 | likely_pathogenic | 0.5414 | ambiguous | -1.186 | Destabilizing | 0.887 | D | 0.591 | neutral | None | None | None | None | N |
| I/D | 0.8879 | likely_pathogenic | 0.8685 | pathogenic | -1.7 | Destabilizing | 0.864 | D | 0.729 | deleterious | None | None | None | None | N |
| I/E | 0.7235 | likely_pathogenic | 0.6714 | pathogenic | -1.596 | Destabilizing | 0.676 | D | 0.719 | prob.delet. | None | None | None | None | N |
| I/F | 0.1903 | likely_benign | 0.1673 | benign | -1.095 | Destabilizing | 0.437 | N | 0.578 | neutral | N | 0.502387134 | None | None | N |
| I/G | 0.7023 | likely_pathogenic | 0.6827 | pathogenic | -2.32 | Highly Destabilizing | 0.676 | D | 0.706 | prob.delet. | None | None | None | None | N |
| I/H | 0.6925 | likely_pathogenic | 0.6319 | pathogenic | -1.457 | Destabilizing | 0.96 | D | 0.752 | deleterious | None | None | None | None | N |
| I/K | 0.6201 | likely_pathogenic | 0.5488 | ambiguous | -1.528 | Destabilizing | 0.676 | D | 0.72 | deleterious | None | None | None | None | N |
| I/L | 0.1033 | likely_benign | 0.1004 | benign | -0.782 | Destabilizing | 0.007 | N | 0.347 | neutral | N | 0.48422266 | None | None | N |
| I/M | 0.0912 | likely_benign | 0.0873 | benign | -0.654 | Destabilizing | 0.02 | N | 0.395 | neutral | D | 0.53159532 | None | None | N |
| I/N | 0.6114 | likely_pathogenic | 0.5621 | ambiguous | -1.571 | Destabilizing | 0.828 | D | 0.754 | deleterious | N | 0.517888822 | None | None | N |
| I/P | 0.938 | likely_pathogenic | 0.9386 | pathogenic | -1.129 | Destabilizing | 0.864 | D | 0.744 | deleterious | None | None | None | None | N |
| I/Q | 0.5958 | likely_pathogenic | 0.5426 | ambiguous | -1.613 | Destabilizing | 0.676 | D | 0.755 | deleterious | None | None | None | None | N |
| I/R | 0.5238 | ambiguous | 0.4541 | ambiguous | -1.002 | Destabilizing | 0.676 | D | 0.746 | deleterious | None | None | None | None | N |
| I/S | 0.3831 | ambiguous | 0.3413 | ambiguous | -2.197 | Highly Destabilizing | 0.181 | N | 0.581 | neutral | N | 0.517381843 | None | None | N |
| I/T | 0.1395 | likely_benign | 0.1134 | benign | -1.963 | Destabilizing | 0.181 | N | 0.586 | neutral | N | 0.504928793 | None | None | N |
| I/V | 0.0496 | likely_benign | 0.0489 | benign | -1.129 | Destabilizing | None | N | 0.144 | neutral | N | 0.38186351 | None | None | N |
| I/W | 0.8593 | likely_pathogenic | 0.825 | pathogenic | -1.287 | Destabilizing | 0.96 | D | 0.776 | deleterious | None | None | None | None | N |
| I/Y | 0.6708 | likely_pathogenic | 0.6223 | pathogenic | -1.036 | Destabilizing | 0.676 | D | 0.619 | neutral | None | None | None | None | N |
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.