Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23199 | 69820;69821;69822 | chr2:178576649;178576648;178576647 | chr2:179441376;179441375;179441374 |
| N2AB | 21558 | 64897;64898;64899 | chr2:178576649;178576648;178576647 | chr2:179441376;179441375;179441374 |
| N2A | 20631 | 62116;62117;62118 | chr2:178576649;178576648;178576647 | chr2:179441376;179441375;179441374 |
| N2B | 14134 | 42625;42626;42627 | chr2:178576649;178576648;178576647 | chr2:179441376;179441375;179441374 |
| Novex-1 | 14259 | 43000;43001;43002 | chr2:178576649;178576648;178576647 | chr2:179441376;179441375;179441374 |
| Novex-2 | 14326 | 43201;43202;43203 | chr2:178576649;178576648;178576647 | chr2:179441376;179441375;179441374 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| C/R | rs943321083  |
-0.554 | 0.794 | N | 0.671 | 0.356 | 0.742569787492 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 6.46E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| C/R | rs943321083 |
-0.554 | 0.794 | N | 0.671 | 0.356 | 0.742569787492 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| C/R | rs943321083 |
-0.554 | 0.794 | N | 0.671 | 0.356 | 0.742569787492 | gnomAD-4.0.0 | 3.04539E-06 | None | None | None | None | N | None | 5.24366E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| C/A | 0.5102 | ambiguous | 0.5197 | ambiguous | -1.494 | Destabilizing | 0.228 | N | 0.331 | neutral | None | None | None | None | N |
| C/D | 0.9311 | likely_pathogenic | 0.9468 | pathogenic | 0.038 | Stabilizing | 0.94 | D | 0.679 | prob.neutral | None | None | None | None | N |
| C/E | 0.9121 | likely_pathogenic | 0.9237 | pathogenic | 0.172 | Stabilizing | 0.836 | D | 0.667 | neutral | None | None | None | None | N |
| C/F | 0.1578 | likely_benign | 0.152 | benign | -0.885 | Destabilizing | 0.001 | N | 0.398 | neutral | N | 0.371254153 | None | None | N |
| C/G | 0.3402 | ambiguous | 0.3673 | ambiguous | -1.814 | Destabilizing | 0.523 | D | 0.612 | neutral | N | 0.505589649 | None | None | N |
| C/H | 0.5434 | ambiguous | 0.5769 | pathogenic | -1.72 | Destabilizing | 0.716 | D | 0.643 | neutral | None | None | None | None | N |
| C/I | 0.4644 | ambiguous | 0.4319 | ambiguous | -0.669 | Destabilizing | 0.129 | N | 0.515 | neutral | None | None | None | None | N |
| C/K | 0.8818 | likely_pathogenic | 0.8946 | pathogenic | -0.587 | Destabilizing | 0.418 | N | 0.667 | neutral | None | None | None | None | N |
| C/L | 0.3593 | ambiguous | 0.3457 | ambiguous | -0.669 | Destabilizing | 0.001 | N | 0.329 | neutral | None | None | None | None | N |
| C/M | 0.5833 | likely_pathogenic | 0.5722 | pathogenic | 0.155 | Stabilizing | 0.716 | D | 0.618 | neutral | None | None | None | None | N |
| C/N | 0.7226 | likely_pathogenic | 0.7686 | pathogenic | -0.797 | Destabilizing | 0.836 | D | 0.671 | neutral | None | None | None | None | N |
| C/P | 0.9936 | likely_pathogenic | 0.9929 | pathogenic | -0.917 | Destabilizing | 0.94 | D | 0.645 | neutral | None | None | None | None | N |
| C/Q | 0.7033 | likely_pathogenic | 0.7431 | pathogenic | -0.568 | Destabilizing | 0.836 | D | 0.64 | neutral | None | None | None | None | N |
| C/R | 0.6096 | likely_pathogenic | 0.6414 | pathogenic | -0.601 | Destabilizing | 0.794 | D | 0.671 | neutral | N | 0.468975701 | None | None | N |
| C/S | 0.4654 | ambiguous | 0.5101 | ambiguous | -1.335 | Destabilizing | 0.351 | N | 0.547 | neutral | N | 0.519153592 | None | None | N |
| C/T | 0.5947 | likely_pathogenic | 0.6018 | pathogenic | -0.998 | Destabilizing | 0.593 | D | 0.547 | neutral | None | None | None | None | N |
| C/V | 0.3785 | ambiguous | 0.3513 | ambiguous | -0.917 | Destabilizing | 0.129 | N | 0.523 | neutral | None | None | None | None | N |
| C/W | 0.4571 | ambiguous | 0.4972 | ambiguous | -0.916 | Destabilizing | 0.794 | D | 0.605 | neutral | N | 0.496700807 | None | None | N |
| C/Y | 0.2135 | likely_benign | 0.2223 | benign | -0.857 | Destabilizing | 0.001 | N | 0.398 | neutral | N | 0.367845702 | 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.