Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 33412 | 100459;100460;100461 | chr2:178536513;178536512;178536511 | chr2:179401240;179401239;179401238 |
| N2AB | 31771 | 95536;95537;95538 | chr2:178536513;178536512;178536511 | chr2:179401240;179401239;179401238 |
| N2A | 30844 | 92755;92756;92757 | chr2:178536513;178536512;178536511 | chr2:179401240;179401239;179401238 |
| N2B | 24347 | 73264;73265;73266 | chr2:178536513;178536512;178536511 | chr2:179401240;179401239;179401238 |
| Novex-1 | 24472 | 73639;73640;73641 | chr2:178536513;178536512;178536511 | chr2:179401240;179401239;179401238 |
| Novex-2 | 24539 | 73840;73841;73842 | chr2:178536513;178536512;178536511 | chr2:179401240;179401239;179401238 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/S | None | None | None | N | 0.162 | 0.06 | 0.166414681773 | gnomAD-4.0.0 | 7.16524E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.24503E-07 | 0 | 0 |
| A/T | rs778297512  |
-1.341 | None | N | 0.175 | 0.046 | 0.264081493735 | gnomAD-2.1.1 | 5.13E-06 | None | None | None | None | N | None | 0 | 3.74E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| A/T | rs778297512 |
-1.341 | None | N | 0.175 | 0.046 | 0.264081493735 | gnomAD-4.0.0 | 7.16523E-07 | None | None | None | None | N | None | 0 | 2.77408E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.387 | ambiguous | 0.3779 | ambiguous | -0.733 | Destabilizing | 0.001 | N | 0.181 | neutral | None | None | None | None | N |
| A/D | 0.4694 | ambiguous | 0.4203 | ambiguous | -1.679 | Destabilizing | 0.117 | N | 0.611 | neutral | N | 0.461145439 | None | None | N |
| A/E | 0.3348 | likely_benign | 0.4489 | ambiguous | -1.584 | Destabilizing | 0.081 | N | 0.615 | neutral | None | None | None | None | N |
| A/F | 0.2806 | likely_benign | 0.3256 | benign | -0.7 | Destabilizing | 0.555 | D | 0.611 | neutral | None | None | None | None | N |
| A/G | 0.168 | likely_benign | 0.1666 | benign | -1.175 | Destabilizing | 0.027 | N | 0.42 | neutral | N | 0.445253267 | None | None | N |
| A/H | 0.4845 | ambiguous | 0.5753 | pathogenic | -1.622 | Destabilizing | 0.824 | D | 0.601 | neutral | None | None | None | None | N |
| A/I | 0.2513 | likely_benign | 0.2725 | benign | 0.143 | Stabilizing | 0.081 | N | 0.638 | neutral | None | None | None | None | N |
| A/K | 0.5949 | likely_pathogenic | 0.729 | pathogenic | -1.115 | Destabilizing | 0.081 | N | 0.617 | neutral | None | None | None | None | N |
| A/L | 0.1687 | likely_benign | 0.1955 | benign | 0.143 | Stabilizing | 0.035 | N | 0.543 | neutral | None | None | None | None | N |
| A/M | 0.2377 | likely_benign | 0.2439 | benign | 0.082 | Stabilizing | 0.555 | D | 0.617 | neutral | None | None | None | None | N |
| A/N | 0.2747 | likely_benign | 0.3164 | benign | -1.132 | Destabilizing | 0.081 | N | 0.613 | neutral | None | None | None | None | N |
| A/P | 0.9338 | likely_pathogenic | 0.9542 | pathogenic | -0.126 | Destabilizing | 0.317 | N | 0.658 | neutral | N | 0.467191729 | None | None | N |
| A/Q | 0.3736 | ambiguous | 0.4463 | ambiguous | -1.095 | Destabilizing | 0.38 | N | 0.636 | neutral | None | None | None | None | N |
| A/R | 0.5013 | ambiguous | 0.6594 | pathogenic | -1.017 | Destabilizing | 0.38 | N | 0.663 | neutral | None | None | None | None | N |
| A/S | 0.0812 | likely_benign | 0.0822 | benign | -1.492 | Destabilizing | None | N | 0.162 | neutral | N | 0.362130451 | None | None | N |
| A/T | 0.0831 | likely_benign | 0.0872 | benign | -1.291 | Destabilizing | None | N | 0.175 | neutral | N | 0.401691703 | None | None | N |
| A/V | 0.1498 | likely_benign | 0.1615 | benign | -0.126 | Destabilizing | 0.062 | N | 0.428 | neutral | N | 0.438500653 | None | None | N |
| A/W | 0.7549 | likely_pathogenic | 0.815 | pathogenic | -1.373 | Destabilizing | 0.935 | D | 0.667 | neutral | None | None | None | None | N |
| A/Y | 0.4402 | ambiguous | 0.5107 | ambiguous | -0.805 | Destabilizing | 0.555 | D | 0.596 | 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.