Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 3002 | 9229;9230;9231 | chr2:178768832;178768831;178768830 | chr2:179633559;179633558;179633557 |
| N2AB | 3002 | 9229;9230;9231 | chr2:178768832;178768831;178768830 | chr2:179633559;179633558;179633557 |
| N2A | 3002 | 9229;9230;9231 | chr2:178768832;178768831;178768830 | chr2:179633559;179633558;179633557 |
| N2B | 2956 | 9091;9092;9093 | chr2:178768832;178768831;178768830 | chr2:179633559;179633558;179633557 |
| Novex-1 | 2956 | 9091;9092;9093 | chr2:178768832;178768831;178768830 | chr2:179633559;179633558;179633557 |
| Novex-2 | 2956 | 9091;9092;9093 | chr2:178768832;178768831;178768830 | chr2:179633559;179633558;179633557 |
| Novex-3 | 3002 | 9229;9230;9231 | chr2:178768832;178768831;178768830 | chr2:179633559;179633558;179633557 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/F | rs1390008829  |
-1.496 | 1.0 | N | 0.644 | 0.29 | 0.353336612579 | gnomAD-2.1.1 | 3.98E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.45E-05 | None | 0 | None | 0 | 0 | 0 |
| L/F | rs1390008829 |
-1.496 | 1.0 | N | 0.644 | 0.29 | 0.353336612579 | gnomAD-4.0.0 | 1.59063E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.77577E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.7925 | likely_pathogenic | 0.8233 | pathogenic | -2.322 | Highly Destabilizing | 0.999 | D | 0.654 | neutral | None | None | None | None | N |
| L/C | 0.7233 | likely_pathogenic | 0.7904 | pathogenic | -1.64 | Destabilizing | 1.0 | D | 0.709 | prob.delet. | None | None | None | None | N |
| L/D | 0.98 | likely_pathogenic | 0.9823 | pathogenic | -2.45 | Highly Destabilizing | 1.0 | D | 0.743 | deleterious | None | None | None | None | N |
| L/E | 0.7513 | likely_pathogenic | 0.7747 | pathogenic | -2.285 | Highly Destabilizing | 1.0 | D | 0.745 | deleterious | None | None | None | None | N |
| L/F | 0.1924 | likely_benign | 0.1986 | benign | -1.424 | Destabilizing | 1.0 | D | 0.644 | neutral | N | 0.439957012 | None | None | N |
| L/G | 0.9348 | likely_pathogenic | 0.9439 | pathogenic | -2.8 | Highly Destabilizing | 1.0 | D | 0.733 | prob.delet. | None | None | None | None | N |
| L/H | 0.5383 | ambiguous | 0.5765 | pathogenic | -2.197 | Highly Destabilizing | 1.0 | D | 0.755 | deleterious | None | None | None | None | N |
| L/I | 0.2271 | likely_benign | 0.2433 | benign | -0.976 | Destabilizing | 0.999 | D | 0.495 | neutral | D | 0.557521077 | None | None | N |
| L/K | 0.5304 | ambiguous | 0.5901 | pathogenic | -1.715 | Destabilizing | 1.0 | D | 0.691 | prob.neutral | None | None | None | None | N |
| L/M | 0.1434 | likely_benign | 0.1635 | benign | -0.944 | Destabilizing | 1.0 | D | 0.67 | neutral | None | None | None | None | N |
| L/N | 0.847 | likely_pathogenic | 0.8702 | pathogenic | -1.904 | Destabilizing | 1.0 | D | 0.749 | deleterious | None | None | None | None | N |
| L/P | 0.9987 | likely_pathogenic | 0.9985 | pathogenic | -1.402 | Destabilizing | 1.0 | D | 0.747 | deleterious | None | None | None | None | N |
| L/Q | 0.3522 | ambiguous | 0.3771 | ambiguous | -1.868 | Destabilizing | 1.0 | D | 0.723 | prob.delet. | None | None | None | None | N |
| L/R | 0.4609 | ambiguous | 0.5055 | ambiguous | -1.332 | Destabilizing | 1.0 | D | 0.73 | prob.delet. | None | None | None | None | N |
| L/S | 0.7743 | likely_pathogenic | 0.8076 | pathogenic | -2.581 | Highly Destabilizing | 1.0 | D | 0.68 | prob.neutral | N | 0.475792257 | None | None | N |
| L/T | 0.5653 | likely_pathogenic | 0.6359 | pathogenic | -2.286 | Highly Destabilizing | 1.0 | D | 0.73 | prob.delet. | None | None | None | None | N |
| L/V | 0.2311 | likely_benign | 0.2593 | benign | -1.402 | Destabilizing | 0.999 | D | 0.511 | neutral | N | 0.517356688 | None | None | N |
| L/W | 0.393 | ambiguous | 0.4386 | ambiguous | -1.753 | Destabilizing | 1.0 | D | 0.729 | prob.delet. | None | None | None | None | N |
| L/Y | 0.4751 | ambiguous | 0.5068 | ambiguous | -1.465 | Destabilizing | 1.0 | D | 0.733 | prob.delet. | 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.