Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 3422 | 10489;10490;10491 | chr2:178759023;178759022;178759021 | chr2:179623750;179623749;179623748 |
| N2AB | 3422 | 10489;10490;10491 | chr2:178759023;178759022;178759021 | chr2:179623750;179623749;179623748 |
| N2A | 3422 | 10489;10490;10491 | chr2:178759023;178759022;178759021 | chr2:179623750;179623749;179623748 |
| N2B | 3376 | 10351;10352;10353 | chr2:178759023;178759022;178759021 | chr2:179623750;179623749;179623748 |
| Novex-1 | 3376 | 10351;10352;10353 | chr2:178759023;178759022;178759021 | chr2:179623750;179623749;179623748 |
| Novex-2 | 3376 | 10351;10352;10353 | chr2:178759023;178759022;178759021 | chr2:179623750;179623749;179623748 |
| Novex-3 | 3422 | 10489;10490;10491 | chr2:178759023;178759022;178759021 | chr2:179623750;179623749;179623748 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/E | None | None | 0.055 | N | 0.572 | 0.289 | 0.653172182626 | gnomAD-4.0.0 | 6.84123E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99345E-07 | 0 | 0 |
| V/G | rs1280394561  |
-0.285 | None | N | 0.453 | 0.233 | 0.624628272354 | gnomAD-2.1.1 | 3.98E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| V/G | rs1280394561 |
-0.285 | None | N | 0.453 | 0.233 | 0.624628272354 | gnomAD-4.0.0 | 6.84123E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.15937E-05 | 0 |
| V/L | None | None | None | N | 0.225 | 0.084 | 0.159798565429 | gnomAD-4.0.0 | 4.80129E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.25001E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.1219 | likely_benign | 0.1129 | benign | -0.386 | Destabilizing | None | N | 0.24 | neutral | N | 0.422125989 | None | None | I |
| V/C | 0.8568 | likely_pathogenic | 0.7826 | pathogenic | -0.848 | Destabilizing | 0.628 | D | 0.524 | neutral | None | None | None | None | I |
| V/D | 0.4917 | ambiguous | 0.3819 | ambiguous | -0.417 | Destabilizing | 0.214 | N | 0.569 | neutral | None | None | None | None | I |
| V/E | 0.3758 | ambiguous | 0.2712 | benign | -0.534 | Destabilizing | 0.055 | N | 0.572 | neutral | N | 0.510848109 | None | None | I |
| V/F | 0.1865 | likely_benign | 0.1524 | benign | -0.797 | Destabilizing | 0.214 | N | 0.507 | neutral | None | None | None | None | I |
| V/G | 0.2945 | likely_benign | 0.2174 | benign | -0.425 | Destabilizing | None | N | 0.453 | neutral | N | 0.471364337 | None | None | I |
| V/H | 0.6551 | likely_pathogenic | 0.5432 | ambiguous | -0.034 | Destabilizing | 0.864 | D | 0.571 | neutral | None | None | None | None | I |
| V/I | 0.089 | likely_benign | 0.0929 | benign | -0.418 | Destabilizing | 0.001 | N | 0.253 | neutral | N | 0.49850162 | None | None | I |
| V/K | 0.4578 | ambiguous | 0.3171 | benign | -0.424 | Destabilizing | 0.072 | N | 0.591 | neutral | None | None | None | None | I |
| V/L | 0.2702 | likely_benign | 0.1899 | benign | -0.418 | Destabilizing | None | N | 0.225 | neutral | N | 0.436164428 | None | None | I |
| V/M | 0.1711 | likely_benign | 0.1062 | benign | -0.648 | Destabilizing | 0.001 | N | 0.343 | neutral | None | None | None | None | I |
| V/N | 0.3939 | ambiguous | 0.3121 | benign | -0.223 | Destabilizing | 0.214 | N | 0.576 | neutral | None | None | None | None | I |
| V/P | 0.8445 | likely_pathogenic | 0.7664 | pathogenic | -0.382 | Destabilizing | 0.356 | N | 0.587 | neutral | None | None | None | None | I |
| V/Q | 0.4089 | ambiguous | 0.2848 | benign | -0.435 | Destabilizing | 0.214 | N | 0.592 | neutral | None | None | None | None | I |
| V/R | 0.3778 | ambiguous | 0.2465 | benign | 0.017 | Stabilizing | 0.214 | N | 0.577 | neutral | None | None | None | None | I |
| V/S | 0.2131 | likely_benign | 0.1687 | benign | -0.525 | Destabilizing | 0.016 | N | 0.578 | neutral | None | None | None | None | I |
| V/T | 0.166 | likely_benign | 0.1405 | benign | -0.556 | Destabilizing | None | N | 0.269 | neutral | None | None | None | None | I |
| V/W | 0.8544 | likely_pathogenic | 0.7367 | pathogenic | -0.836 | Destabilizing | 0.864 | D | 0.569 | neutral | None | None | None | None | I |
| V/Y | 0.6498 | likely_pathogenic | 0.537 | ambiguous | -0.581 | Destabilizing | 0.356 | N | 0.509 | 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.