Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 33670 | 101233;101234;101235 | chr2:178535607;178535606;178535605 | chr2:179400334;179400333;179400332 |
| N2AB | 32029 | 96310;96311;96312 | chr2:178535607;178535606;178535605 | chr2:179400334;179400333;179400332 |
| N2A | 31102 | 93529;93530;93531 | chr2:178535607;178535606;178535605 | chr2:179400334;179400333;179400332 |
| N2B | 24605 | 74038;74039;74040 | chr2:178535607;178535606;178535605 | chr2:179400334;179400333;179400332 |
| Novex-1 | 24730 | 74413;74414;74415 | chr2:178535607;178535606;178535605 | chr2:179400334;179400333;179400332 |
| Novex-2 | 24797 | 74614;74615;74616 | chr2:178535607;178535606;178535605 | chr2:179400334;179400333;179400332 |
| 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/Y | rs749219080  |
-1.7 | 1.0 | N | 0.749 | 0.334 | 0.720504425005 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.89E-06 | 0 |
| C/Y | rs749219080 |
-1.7 | 1.0 | N | 0.749 | 0.334 | 0.720504425005 | gnomAD-4.0.0 | 2.73678E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.59781E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| C/A | 0.7148 | likely_pathogenic | 0.5521 | ambiguous | -1.503 | Destabilizing | 0.986 | D | 0.592 | neutral | None | None | None | None | N |
| C/D | 0.9838 | likely_pathogenic | 0.931 | pathogenic | -1.121 | Destabilizing | 1.0 | D | 0.769 | deleterious | None | None | None | None | N |
| C/E | 0.9822 | likely_pathogenic | 0.9237 | pathogenic | -1.002 | Destabilizing | 1.0 | D | 0.769 | deleterious | None | None | None | None | N |
| C/F | 0.645 | likely_pathogenic | 0.4088 | ambiguous | -0.942 | Destabilizing | 1.0 | D | 0.751 | deleterious | N | 0.453577253 | None | None | N |
| C/G | 0.6437 | likely_pathogenic | 0.4649 | ambiguous | -1.81 | Destabilizing | 0.995 | D | 0.757 | deleterious | N | 0.496597312 | None | None | N |
| C/H | 0.9157 | likely_pathogenic | 0.7321 | pathogenic | -2.082 | Highly Destabilizing | 1.0 | D | 0.739 | prob.delet. | None | None | None | None | N |
| C/I | 0.8056 | likely_pathogenic | 0.6395 | pathogenic | -0.717 | Destabilizing | 0.997 | D | 0.713 | prob.delet. | None | None | None | None | N |
| C/K | 0.981 | likely_pathogenic | 0.9196 | pathogenic | -1.233 | Destabilizing | 1.0 | D | 0.772 | deleterious | None | None | None | None | N |
| C/L | 0.7749 | likely_pathogenic | 0.6258 | pathogenic | -0.717 | Destabilizing | 0.997 | D | 0.663 | neutral | None | None | None | None | N |
| C/M | 0.7919 | likely_pathogenic | 0.6567 | pathogenic | 0.155 | Stabilizing | 0.993 | D | 0.549 | neutral | None | None | None | None | N |
| C/N | 0.8819 | likely_pathogenic | 0.6927 | pathogenic | -1.306 | Destabilizing | 1.0 | D | 0.767 | deleterious | None | None | None | None | N |
| C/P | 0.999 | likely_pathogenic | 0.9984 | pathogenic | -0.953 | Destabilizing | 1.0 | D | 0.771 | deleterious | None | None | None | None | N |
| C/Q | 0.9191 | likely_pathogenic | 0.7744 | pathogenic | -1.194 | Destabilizing | 1.0 | D | 0.771 | deleterious | None | None | None | None | N |
| C/R | 0.9049 | likely_pathogenic | 0.7081 | pathogenic | -1.199 | Destabilizing | 1.0 | D | 0.771 | deleterious | N | 0.417365737 | None | None | N |
| C/S | 0.6319 | likely_pathogenic | 0.3855 | ambiguous | -1.699 | Destabilizing | 0.985 | D | 0.703 | prob.neutral | N | 0.433951343 | None | None | N |
| C/T | 0.6497 | likely_pathogenic | 0.4184 | ambiguous | -1.417 | Destabilizing | 0.489 | N | 0.427 | neutral | None | None | None | None | N |
| C/V | 0.6598 | likely_pathogenic | 0.5094 | ambiguous | -0.953 | Destabilizing | 0.98 | D | 0.685 | prob.neutral | None | None | None | None | N |
| C/W | 0.9233 | likely_pathogenic | 0.797 | pathogenic | -1.127 | Destabilizing | 1.0 | D | 0.712 | prob.delet. | N | 0.497290745 | None | None | N |
| C/Y | 0.8369 | likely_pathogenic | 0.5827 | pathogenic | -1.013 | Destabilizing | 1.0 | D | 0.749 | deleterious | N | 0.459599149 | 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.