Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23447 | 70564;70565;70566 | chr2:178575793;178575792;178575791 | chr2:179440520;179440519;179440518 |
| N2AB | 21806 | 65641;65642;65643 | chr2:178575793;178575792;178575791 | chr2:179440520;179440519;179440518 |
| N2A | 20879 | 62860;62861;62862 | chr2:178575793;178575792;178575791 | chr2:179440520;179440519;179440518 |
| N2B | 14382 | 43369;43370;43371 | chr2:178575793;178575792;178575791 | chr2:179440520;179440519;179440518 |
| Novex-1 | 14507 | 43744;43745;43746 | chr2:178575793;178575792;178575791 | chr2:179440520;179440519;179440518 |
| Novex-2 | 14574 | 43945;43946;43947 | chr2:178575793;178575792;178575791 | chr2:179440520;179440519;179440518 |
| 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/M | rs1213801020  |
-0.694 | 0.942 | N | 0.517 | 0.402 | 0.43126412278 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| I/M | rs1213801020 |
-0.694 | 0.942 | N | 0.517 | 0.402 | 0.43126412278 | gnomAD-4.0.0 | 4.10714E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 5.7975E-05 | 1.65722E-05 |
| I/V | None | None | 0.006 | N | 0.175 | 0.085 | 0.261217442401 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 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 | 0.4455 | ambiguous | 0.4319 | ambiguous | -1.026 | Destabilizing | 0.754 | D | 0.487 | neutral | None | None | None | None | N |
| I/C | 0.6598 | likely_pathogenic | 0.6389 | pathogenic | -1.012 | Destabilizing | 0.998 | D | 0.603 | neutral | None | None | None | None | N |
| I/D | 0.9205 | likely_pathogenic | 0.9262 | pathogenic | -0.533 | Destabilizing | 0.993 | D | 0.727 | prob.delet. | None | None | None | None | N |
| I/E | 0.8235 | likely_pathogenic | 0.8476 | pathogenic | -0.585 | Destabilizing | 0.978 | D | 0.733 | prob.delet. | None | None | None | None | N |
| I/F | 0.2877 | likely_benign | 0.2905 | benign | -1.183 | Destabilizing | 0.942 | D | 0.529 | neutral | N | 0.479881615 | None | None | N |
| I/G | 0.7912 | likely_pathogenic | 0.7902 | pathogenic | -1.224 | Destabilizing | 0.978 | D | 0.717 | prob.delet. | None | None | None | None | N |
| I/H | 0.7454 | likely_pathogenic | 0.7615 | pathogenic | -0.742 | Destabilizing | 0.998 | D | 0.714 | prob.delet. | None | None | None | None | N |
| I/K | 0.5638 | ambiguous | 0.5975 | pathogenic | -0.443 | Destabilizing | 0.978 | D | 0.732 | prob.delet. | None | None | None | None | N |
| I/L | 0.2031 | likely_benign | 0.1883 | benign | -0.595 | Destabilizing | 0.294 | N | 0.296 | neutral | N | 0.50131998 | None | None | N |
| I/M | 0.1496 | likely_benign | 0.1523 | benign | -0.507 | Destabilizing | 0.942 | D | 0.517 | neutral | N | 0.496073313 | None | None | N |
| I/N | 0.5485 | ambiguous | 0.5795 | pathogenic | -0.296 | Destabilizing | 0.99 | D | 0.732 | prob.delet. | N | 0.498933695 | None | None | N |
| I/P | 0.8493 | likely_pathogenic | 0.844 | pathogenic | -0.708 | Destabilizing | 0.993 | D | 0.734 | prob.delet. | None | None | None | None | N |
| I/Q | 0.6691 | likely_pathogenic | 0.692 | pathogenic | -0.55 | Destabilizing | 0.993 | D | 0.73 | prob.delet. | None | None | None | None | N |
| I/R | 0.4918 | ambiguous | 0.5255 | ambiguous | -0.024 | Destabilizing | 0.978 | D | 0.731 | prob.delet. | None | None | None | None | N |
| I/S | 0.4736 | ambiguous | 0.4764 | ambiguous | -0.846 | Destabilizing | 0.942 | D | 0.623 | neutral | N | 0.479766257 | None | None | N |
| I/T | 0.2259 | likely_benign | 0.2475 | benign | -0.79 | Destabilizing | 0.822 | D | 0.527 | neutral | N | 0.484697089 | None | None | N |
| I/V | 0.0636 | likely_benign | 0.0636 | benign | -0.708 | Destabilizing | 0.006 | N | 0.175 | neutral | N | 0.400134265 | None | None | N |
| I/W | 0.9158 | likely_pathogenic | 0.9153 | pathogenic | -1.208 | Destabilizing | 0.998 | D | 0.705 | prob.neutral | None | None | None | None | N |
| I/Y | 0.7234 | likely_pathogenic | 0.7223 | pathogenic | -0.864 | Destabilizing | 0.978 | D | 0.624 | 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.