Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1741 | 5446;5447;5448 | chr2:178776643;178776642;178776641 | chr2:179641370;179641369;179641368 |
| N2AB | 1741 | 5446;5447;5448 | chr2:178776643;178776642;178776641 | chr2:179641370;179641369;179641368 |
| N2A | 1741 | 5446;5447;5448 | chr2:178776643;178776642;178776641 | chr2:179641370;179641369;179641368 |
| N2B | 1695 | 5308;5309;5310 | chr2:178776643;178776642;178776641 | chr2:179641370;179641369;179641368 |
| Novex-1 | 1695 | 5308;5309;5310 | chr2:178776643;178776642;178776641 | chr2:179641370;179641369;179641368 |
| Novex-2 | 1695 | 5308;5309;5310 | chr2:178776643;178776642;178776641 | chr2:179641370;179641369;179641368 |
| Novex-3 | 1741 | 5446;5447;5448 | chr2:178776643;178776642;178776641 | chr2:179641370;179641369;179641368 |
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 | rs376751465  |
-0.378 | 1.0 | N | 0.637 | 0.815 | None | gnomAD-2.1.1 | 3.99E-06 | None | None | None | None | N | None | 6.15E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| D/G | rs376751465 |
-0.378 | 1.0 | N | 0.637 | 0.815 | None | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| D/G | rs376751465 |
-0.378 | 1.0 | N | 0.637 | 0.815 | None | gnomAD-4.0.0 | 6.56901E-06 | None | None | None | None | N | None | 2.41243E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| D/V | None | None | 1.0 | D | 0.672 | 0.889 | 0.841363702225 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.75482E-04 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.8583 | likely_pathogenic | 0.8637 | pathogenic | -0.363 | Destabilizing | 1.0 | D | 0.689 | prob.neutral | D | 0.591431015 | None | None | N |
| D/C | 0.9828 | likely_pathogenic | 0.9826 | pathogenic | 0.028 | Stabilizing | 1.0 | D | 0.629 | neutral | None | None | None | None | N |
| D/E | 0.6527 | likely_pathogenic | 0.6866 | pathogenic | -0.278 | Destabilizing | 1.0 | D | 0.415 | neutral | D | 0.523798626 | None | None | N |
| D/F | 0.9904 | likely_pathogenic | 0.9915 | pathogenic | -0.329 | Destabilizing | 1.0 | D | 0.614 | neutral | None | None | None | None | N |
| D/G | 0.6881 | likely_pathogenic | 0.6954 | pathogenic | -0.562 | Destabilizing | 1.0 | D | 0.637 | neutral | N | 0.520250513 | None | None | N |
| D/H | 0.9306 | likely_pathogenic | 0.935 | pathogenic | -0.23 | Destabilizing | 1.0 | D | 0.57 | neutral | D | 0.671506247 | None | None | N |
| D/I | 0.9913 | likely_pathogenic | 0.9918 | pathogenic | 0.118 | Stabilizing | 1.0 | D | 0.645 | neutral | None | None | None | None | N |
| D/K | 0.9656 | likely_pathogenic | 0.9687 | pathogenic | 0.175 | Stabilizing | 1.0 | D | 0.661 | neutral | None | None | None | None | N |
| D/L | 0.9665 | likely_pathogenic | 0.9692 | pathogenic | 0.118 | Stabilizing | 1.0 | D | 0.671 | neutral | None | None | None | None | N |
| D/M | 0.9903 | likely_pathogenic | 0.991 | pathogenic | 0.323 | Stabilizing | 1.0 | D | 0.623 | neutral | None | None | None | None | N |
| D/N | 0.34 | likely_benign | 0.3516 | ambiguous | -0.044 | Destabilizing | 1.0 | D | 0.599 | neutral | N | 0.395760768 | None | None | N |
| D/P | 0.9982 | likely_pathogenic | 0.9984 | pathogenic | -0.02 | Destabilizing | 1.0 | D | 0.631 | neutral | None | None | None | None | N |
| D/Q | 0.9127 | likely_pathogenic | 0.9246 | pathogenic | -0.015 | Destabilizing | 1.0 | D | 0.619 | neutral | None | None | None | None | N |
| D/R | 0.9529 | likely_pathogenic | 0.9573 | pathogenic | 0.336 | Stabilizing | 1.0 | D | 0.654 | neutral | None | None | None | None | N |
| D/S | 0.5883 | likely_pathogenic | 0.59 | pathogenic | -0.186 | Destabilizing | 1.0 | D | 0.613 | neutral | None | None | None | None | N |
| D/T | 0.9509 | likely_pathogenic | 0.9507 | pathogenic | -0.034 | Destabilizing | 1.0 | D | 0.674 | neutral | None | None | None | None | N |
| D/V | 0.9716 | likely_pathogenic | 0.9728 | pathogenic | -0.02 | Destabilizing | 1.0 | D | 0.672 | neutral | D | 0.672052403 | None | None | N |
| D/W | 0.9981 | likely_pathogenic | 0.9983 | pathogenic | -0.204 | Destabilizing | 1.0 | D | 0.64 | neutral | None | None | None | None | N |
| D/Y | 0.9347 | likely_pathogenic | 0.9407 | pathogenic | -0.103 | Destabilizing | 1.0 | D | 0.601 | neutral | D | 0.710078624 | 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.