Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20398 | 61417;61418;61419 | chr2:178590533;178590532;178590531 | chr2:179455260;179455259;179455258 |
| N2AB | 18757 | 56494;56495;56496 | chr2:178590533;178590532;178590531 | chr2:179455260;179455259;179455258 |
| N2A | 17830 | 53713;53714;53715 | chr2:178590533;178590532;178590531 | chr2:179455260;179455259;179455258 |
| N2B | 11333 | 34222;34223;34224 | chr2:178590533;178590532;178590531 | chr2:179455260;179455259;179455258 |
| Novex-1 | 11458 | 34597;34598;34599 | chr2:178590533;178590532;178590531 | chr2:179455260;179455259;179455258 |
| Novex-2 | 11525 | 34798;34799;34800 | chr2:178590533;178590532;178590531 | chr2:179455260;179455259;179455258 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/G | rs756486468  |
-0.856 | 0.996 | N | 0.681 | 0.5 | 0.513448892127 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.92E-06 | 0 |
| D/H | None | None | 1.0 | N | 0.664 | 0.415 | 0.533567079455 | gnomAD-4.0.0 | 1.59323E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86172E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.9504 | likely_pathogenic | 0.9578 | pathogenic | -0.416 | Destabilizing | 0.998 | D | 0.665 | neutral | N | 0.501122514 | None | None | I |
| D/C | 0.9877 | likely_pathogenic | 0.9885 | pathogenic | 0.189 | Stabilizing | 1.0 | D | 0.645 | neutral | None | None | None | None | I |
| D/E | 0.8976 | likely_pathogenic | 0.9049 | pathogenic | -0.386 | Destabilizing | 0.275 | N | 0.251 | neutral | N | 0.500108556 | None | None | I |
| D/F | 0.9925 | likely_pathogenic | 0.9929 | pathogenic | -0.568 | Destabilizing | 1.0 | D | 0.643 | neutral | None | None | None | None | I |
| D/G | 0.9416 | likely_pathogenic | 0.947 | pathogenic | -0.624 | Destabilizing | 0.996 | D | 0.681 | prob.neutral | N | 0.515974767 | None | None | I |
| D/H | 0.9669 | likely_pathogenic | 0.9689 | pathogenic | -0.779 | Destabilizing | 1.0 | D | 0.664 | neutral | N | 0.501882983 | None | None | I |
| D/I | 0.9907 | likely_pathogenic | 0.9912 | pathogenic | 0.089 | Stabilizing | 1.0 | D | 0.678 | prob.neutral | None | None | None | None | I |
| D/K | 0.9879 | likely_pathogenic | 0.9882 | pathogenic | 0.321 | Stabilizing | 0.996 | D | 0.667 | neutral | None | None | None | None | I |
| D/L | 0.9852 | likely_pathogenic | 0.9862 | pathogenic | 0.089 | Stabilizing | 0.999 | D | 0.669 | neutral | None | None | None | None | I |
| D/M | 0.9951 | likely_pathogenic | 0.9956 | pathogenic | 0.494 | Stabilizing | 1.0 | D | 0.633 | neutral | None | None | None | None | I |
| D/N | 0.4739 | ambiguous | 0.4453 | ambiguous | 0.057 | Stabilizing | 0.998 | D | 0.727 | prob.delet. | N | 0.510112822 | None | None | I |
| D/P | 0.9899 | likely_pathogenic | 0.9919 | pathogenic | -0.057 | Destabilizing | 0.999 | D | 0.709 | prob.delet. | None | None | None | None | I |
| D/Q | 0.9809 | likely_pathogenic | 0.9837 | pathogenic | 0.082 | Stabilizing | 0.998 | D | 0.737 | prob.delet. | None | None | None | None | I |
| D/R | 0.9858 | likely_pathogenic | 0.9869 | pathogenic | 0.231 | Stabilizing | 0.998 | D | 0.684 | prob.neutral | None | None | None | None | I |
| D/S | 0.7839 | likely_pathogenic | 0.7953 | pathogenic | -0.057 | Destabilizing | 0.994 | D | 0.689 | prob.neutral | None | None | None | None | I |
| D/T | 0.9183 | likely_pathogenic | 0.9184 | pathogenic | 0.113 | Stabilizing | 0.999 | D | 0.712 | prob.delet. | None | None | None | None | I |
| D/V | 0.9715 | likely_pathogenic | 0.9726 | pathogenic | -0.057 | Destabilizing | 0.999 | D | 0.676 | prob.neutral | N | 0.507959369 | None | None | I |
| D/W | 0.9981 | likely_pathogenic | 0.9983 | pathogenic | -0.48 | Destabilizing | 1.0 | D | 0.658 | neutral | None | None | None | None | I |
| D/Y | 0.9524 | likely_pathogenic | 0.9557 | pathogenic | -0.338 | Destabilizing | 1.0 | D | 0.643 | neutral | D | 0.538851962 | 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.