Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1516 | 4771;4772;4773 | chr2:178777519;178777518;178777517 | chr2:179642246;179642245;179642244 |
| N2AB | 1516 | 4771;4772;4773 | chr2:178777519;178777518;178777517 | chr2:179642246;179642245;179642244 |
| N2A | 1516 | 4771;4772;4773 | chr2:178777519;178777518;178777517 | chr2:179642246;179642245;179642244 |
| N2B | 1470 | 4633;4634;4635 | chr2:178777519;178777518;178777517 | chr2:179642246;179642245;179642244 |
| Novex-1 | 1470 | 4633;4634;4635 | chr2:178777519;178777518;178777517 | chr2:179642246;179642245;179642244 |
| Novex-2 | 1470 | 4633;4634;4635 | chr2:178777519;178777518;178777517 | chr2:179642246;179642245;179642244 |
| Novex-3 | 1516 | 4771;4772;4773 | chr2:178777519;178777518;178777517 | chr2:179642246;179642245;179642244 |
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/F | None | None | 0.468 | D | 0.595 | 0.347 | 0.679497533952 | gnomAD-4.0.0 | 6.84197E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99358E-07 | 0 | 0 |
| I/T | rs1464496143  |
-2.177 | 0.638 | N | 0.623 | 0.396 | 0.741560904565 | gnomAD-2.1.1 | 3.99E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.83E-06 | 0 |
| I/T | rs1464496143 |
-2.177 | 0.638 | N | 0.623 | 0.396 | 0.741560904565 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| I/T | rs1464496143 |
-2.177 | 0.638 | N | 0.623 | 0.396 | 0.741560904565 | gnomAD-4.0.0 | 1.48716E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.03398E-05 | 0 | 0 |
| I/V | rs1184288875 |
-1.324 | 0.043 | N | 0.399 | 0.116 | None | gnomAD-2.1.1 | 1.77E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 3.89E-05 | 0 |
| I/V | rs1184288875 |
-1.324 | 0.043 | N | 0.399 | 0.116 | None | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 4.41E-05 | 0 | 0 |
| I/V | rs1184288875 |
-1.324 | 0.043 | N | 0.399 | 0.116 | None | gnomAD-4.0.0 | 4.46156E-05 | None | None | None | None | I | None | 1.33476E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 6.01726E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.975 | likely_pathogenic | 0.9765 | pathogenic | -2.188 | Highly Destabilizing | 0.399 | N | 0.519 | neutral | None | None | None | None | I |
| I/C | 0.9892 | likely_pathogenic | 0.9875 | pathogenic | -1.524 | Destabilizing | 0.982 | D | 0.675 | neutral | None | None | None | None | I |
| I/D | 0.9983 | likely_pathogenic | 0.9983 | pathogenic | -2.009 | Highly Destabilizing | 0.935 | D | 0.749 | deleterious | None | None | None | None | I |
| I/E | 0.9921 | likely_pathogenic | 0.9923 | pathogenic | -1.923 | Destabilizing | 0.826 | D | 0.737 | prob.delet. | None | None | None | None | I |
| I/F | 0.757 | likely_pathogenic | 0.7328 | pathogenic | -1.378 | Destabilizing | 0.468 | N | 0.595 | neutral | D | 0.54316132 | None | None | I |
| I/G | 0.9958 | likely_pathogenic | 0.996 | pathogenic | -2.598 | Highly Destabilizing | 0.826 | D | 0.725 | prob.delet. | None | None | None | None | I |
| I/H | 0.9848 | likely_pathogenic | 0.984 | pathogenic | -1.818 | Destabilizing | 0.982 | D | 0.73 | prob.delet. | None | None | None | None | I |
| I/K | 0.9854 | likely_pathogenic | 0.9841 | pathogenic | -1.575 | Destabilizing | 0.826 | D | 0.729 | prob.delet. | None | None | None | None | I |
| I/L | 0.4336 | ambiguous | 0.406 | ambiguous | -1.073 | Destabilizing | 0.001 | N | 0.253 | neutral | N | 0.502574004 | None | None | I |
| I/M | 0.4101 | ambiguous | 0.3826 | ambiguous | -0.976 | Destabilizing | 0.468 | N | 0.62 | neutral | D | 0.533365599 | None | None | I |
| I/N | 0.9709 | likely_pathogenic | 0.9705 | pathogenic | -1.55 | Destabilizing | 0.916 | D | 0.753 | deleterious | N | 0.502501557 | None | None | I |
| I/P | 0.9983 | likely_pathogenic | 0.9984 | pathogenic | -1.419 | Destabilizing | 0.935 | D | 0.753 | deleterious | None | None | None | None | I |
| I/Q | 0.9727 | likely_pathogenic | 0.9722 | pathogenic | -1.649 | Destabilizing | 0.935 | D | 0.751 | deleterious | None | None | None | None | I |
| I/R | 0.968 | likely_pathogenic | 0.9653 | pathogenic | -1.053 | Destabilizing | 0.826 | D | 0.753 | deleterious | None | None | None | None | I |
| I/S | 0.9692 | likely_pathogenic | 0.9705 | pathogenic | -2.231 | Highly Destabilizing | 0.781 | D | 0.665 | neutral | N | 0.50374829 | None | None | I |
| I/T | 0.9588 | likely_pathogenic | 0.9583 | pathogenic | -2.026 | Highly Destabilizing | 0.638 | D | 0.623 | neutral | N | 0.500416693 | None | None | I |
| I/V | 0.4249 | ambiguous | 0.4214 | ambiguous | -1.419 | Destabilizing | 0.043 | N | 0.399 | neutral | N | 0.507159998 | None | None | I |
| I/W | 0.9874 | likely_pathogenic | 0.985 | pathogenic | -1.547 | Destabilizing | 0.982 | D | 0.7 | prob.neutral | None | None | None | None | I |
| I/Y | 0.9569 | likely_pathogenic | 0.956 | pathogenic | -1.321 | Destabilizing | 0.826 | D | 0.687 | prob.neutral | None | None | 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.