Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 3163 | 9712;9713;9714 | chr2:178766597;178766596;178766595 | chr2:179631324;179631323;179631322 |
| N2AB | 3163 | 9712;9713;9714 | chr2:178766597;178766596;178766595 | chr2:179631324;179631323;179631322 |
| N2A | 3163 | 9712;9713;9714 | chr2:178766597;178766596;178766595 | chr2:179631324;179631323;179631322 |
| N2B | 3117 | 9574;9575;9576 | chr2:178766597;178766596;178766595 | chr2:179631324;179631323;179631322 |
| Novex-1 | 3117 | 9574;9575;9576 | chr2:178766597;178766596;178766595 | chr2:179631324;179631323;179631322 |
| Novex-2 | 3117 | 9574;9575;9576 | chr2:178766597;178766596;178766595 | chr2:179631324;179631323;179631322 |
| Novex-3 | 3163 | 9712;9713;9714 | chr2:178766597;178766596;178766595 | chr2:179631324;179631323;179631322 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/C | rs140664731  |
-0.192 | 1.0 | N | 0.788 | 0.559 | None | gnomAD-2.1.1 | 1.31282E-04 | None | None | None | None | N | None | 1.08147E-03 | 2.83E-05 | None | 0 | 4.02293E-04 | None | 0 | None | 0 | 7.79E-06 | 0 |
| R/C | rs140664731 |
-0.192 | 1.0 | N | 0.788 | 0.559 | None | gnomAD-3.1.2 | 2.82668E-04 | None | None | None | None | N | None | 8.9303E-04 | 1.96412E-04 | 0 | 0 | 5.76701E-04 | None | 0 | 0 | 0 | 0 | 0 |
| R/C | rs140664731 |
-0.192 | 1.0 | N | 0.788 | 0.559 | None | 1000 genomes | 5.99042E-04 | None | None | None | None | N | None | 1.5E-03 | 0 | None | None | 1E-03 | 0 | None | None | None | 0 | None |
| R/C | rs140664731 |
-0.192 | 1.0 | N | 0.788 | 0.559 | None | gnomAD-4.0.0 | 5.94957E-05 | None | None | None | None | N | None | 9.19755E-04 | 4.9995E-05 | None | 0 | 2.45339E-04 | None | 0 | 0 | 4.23845E-06 | 3.29395E-05 | 8.00102E-05 |
| R/H | rs149755500 |
-0.887 | 1.0 | D | 0.767 | 0.514 | None | gnomAD-2.1.1 | 1.9159E-04 | None | None | None | None | N | None | 3.20436E-04 | 0 | None | 0 | 0 | None | 6.54E-05 | None | 0 | 3.42695E-04 | 0 |
| R/H | rs149755500 |
-0.887 | 1.0 | D | 0.767 | 0.514 | None | gnomAD-3.1.2 | 3.35147E-04 | None | None | None | None | N | None | 6.27353E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 3.67528E-04 | 0 | 0 |
| R/H | rs149755500 |
-0.887 | 1.0 | D | 0.767 | 0.514 | None | gnomAD-4.0.0 | 3.39749E-04 | None | None | None | None | N | None | 5.20583E-04 | 0 | None | 0 | 2.22975E-05 | None | 0 | 0 | 4.03678E-04 | 3.29424E-05 | 4.64416E-04 |
| R/S | rs140664731 |
-0.246 | 1.0 | N | 0.707 | 0.329 | 0.449283877778 | gnomAD-2.1.1 | 3.99E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.85E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.6048 | likely_pathogenic | 0.6579 | pathogenic | -0.566 | Destabilizing | 0.999 | D | 0.606 | neutral | None | None | None | None | N |
| R/C | 0.4216 | ambiguous | 0.5389 | ambiguous | -0.695 | Destabilizing | 1.0 | D | 0.788 | deleterious | N | 0.503210427 | None | None | N |
| R/D | 0.8103 | likely_pathogenic | 0.8376 | pathogenic | 0.041 | Stabilizing | 1.0 | D | 0.739 | prob.delet. | None | None | None | None | N |
| R/E | 0.4838 | ambiguous | 0.554 | ambiguous | 0.154 | Stabilizing | 0.999 | D | 0.663 | neutral | None | None | None | None | N |
| R/F | 0.7798 | likely_pathogenic | 0.8409 | pathogenic | -0.576 | Destabilizing | 1.0 | D | 0.745 | deleterious | None | None | None | None | N |
| R/G | 0.5227 | ambiguous | 0.6028 | pathogenic | -0.826 | Destabilizing | 1.0 | D | 0.635 | neutral | N | 0.509462071 | None | None | N |
| R/H | 0.1709 | likely_benign | 0.2049 | benign | -1.195 | Destabilizing | 1.0 | D | 0.767 | deleterious | D | 0.593252562 | None | None | N |
| R/I | 0.4853 | ambiguous | 0.5839 | pathogenic | 0.113 | Stabilizing | 1.0 | D | 0.752 | deleterious | None | None | None | None | N |
| R/K | 0.1757 | likely_benign | 0.1833 | benign | -0.492 | Destabilizing | 0.998 | D | 0.537 | neutral | None | None | None | None | N |
| R/L | 0.397 | ambiguous | 0.4642 | ambiguous | 0.113 | Stabilizing | 1.0 | D | 0.635 | neutral | D | 0.592179114 | None | None | N |
| R/M | 0.4356 | ambiguous | 0.5376 | ambiguous | -0.347 | Destabilizing | 1.0 | D | 0.758 | deleterious | None | None | None | None | N |
| R/N | 0.7169 | likely_pathogenic | 0.7361 | pathogenic | -0.231 | Destabilizing | 1.0 | D | 0.75 | deleterious | None | None | None | None | N |
| R/P | 0.7222 | likely_pathogenic | 0.7033 | pathogenic | -0.093 | Destabilizing | 1.0 | D | 0.729 | prob.delet. | N | 0.501602709 | None | None | N |
| R/Q | 0.1563 | likely_benign | 0.1721 | benign | -0.327 | Destabilizing | 1.0 | D | 0.739 | prob.delet. | None | None | None | None | N |
| R/S | 0.7055 | likely_pathogenic | 0.7533 | pathogenic | -0.875 | Destabilizing | 1.0 | D | 0.707 | prob.neutral | N | 0.498902553 | None | None | N |
| R/T | 0.4205 | ambiguous | 0.4807 | ambiguous | -0.588 | Destabilizing | 1.0 | D | 0.699 | prob.neutral | None | None | None | None | N |
| R/V | 0.5533 | ambiguous | 0.6159 | pathogenic | -0.093 | Destabilizing | 1.0 | D | 0.741 | deleterious | None | None | None | None | N |
| R/W | 0.3244 | likely_benign | 0.442 | ambiguous | -0.401 | Destabilizing | 1.0 | D | 0.796 | deleterious | None | None | None | None | N |
| R/Y | 0.5866 | likely_pathogenic | 0.6647 | pathogenic | -0.063 | Destabilizing | 1.0 | D | 0.755 | deleterious | 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.