Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1012 | 3259;3260;3261 | chr2:178782872;178782871;178782870 | chr2:179647599;179647598;179647597 |
| N2AB | 1012 | 3259;3260;3261 | chr2:178782872;178782871;178782870 | chr2:179647599;179647598;179647597 |
| N2A | 1012 | 3259;3260;3261 | chr2:178782872;178782871;178782870 | chr2:179647599;179647598;179647597 |
| N2B | 966 | 3121;3122;3123 | chr2:178782872;178782871;178782870 | chr2:179647599;179647598;179647597 |
| Novex-1 | 966 | 3121;3122;3123 | chr2:178782872;178782871;178782870 | chr2:179647599;179647598;179647597 |
| Novex-2 | 966 | 3121;3122;3123 | chr2:178782872;178782871;178782870 | chr2:179647599;179647598;179647597 |
| Novex-3 | 1012 | 3259;3260;3261 | chr2:178782872;178782871;178782870 | chr2:179647599;179647598;179647597 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/Q | rs368885310  |
-0.274 | 0.997 | N | 0.674 | 0.296 | None | gnomAD-2.1.1 | 3.9E-05 | None | None | None | None | N | None | 2.00385E-04 | 0 | None | 0 | 5.03E-05 | None | 9.8E-05 | None | 0 | 1.55E-05 | 0 |
| R/Q | rs368885310 |
-0.274 | 0.997 | N | 0.674 | 0.296 | None | gnomAD-3.1.2 | 5.26E-05 | None | None | None | None | N | None | 1.44893E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 2.07297E-04 | 0 |
| R/Q | rs368885310 |
-0.274 | 0.997 | N | 0.674 | 0.296 | None | gnomAD-4.0.0 | 2.04468E-05 | None | None | None | None | N | None | 2.13322E-04 | 0 | None | 0 | 8.91822E-05 | None | 0 | 0 | 5.08498E-06 | 6.58819E-05 | 1.60015E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.949 | likely_pathogenic | 0.9343 | pathogenic | -0.994 | Destabilizing | 0.953 | D | 0.645 | neutral | None | None | None | None | N |
| R/C | 0.7032 | likely_pathogenic | 0.6953 | pathogenic | -0.92 | Destabilizing | 0.999 | D | 0.747 | deleterious | None | None | None | None | N |
| R/D | 0.9806 | likely_pathogenic | 0.9768 | pathogenic | -0.049 | Destabilizing | 0.986 | D | 0.743 | deleterious | None | None | None | None | N |
| R/E | 0.9087 | likely_pathogenic | 0.8816 | pathogenic | 0.068 | Stabilizing | 0.91 | D | 0.617 | neutral | None | None | None | None | N |
| R/F | 0.9543 | likely_pathogenic | 0.9439 | pathogenic | -0.913 | Destabilizing | 0.998 | D | 0.752 | deleterious | None | None | None | None | N |
| R/G | 0.9345 | likely_pathogenic | 0.9152 | pathogenic | -1.289 | Destabilizing | 0.975 | D | 0.662 | neutral | N | 0.51318875 | None | None | N |
| R/H | 0.3013 | likely_benign | 0.2879 | benign | -1.523 | Destabilizing | 0.998 | D | 0.702 | prob.neutral | None | None | None | None | N |
| R/I | 0.8031 | likely_pathogenic | 0.7514 | pathogenic | -0.201 | Destabilizing | 0.993 | D | 0.767 | deleterious | None | None | None | None | N |
| R/K | 0.3904 | ambiguous | 0.3771 | ambiguous | -0.906 | Destabilizing | 0.06 | N | 0.309 | neutral | None | None | None | None | N |
| R/L | 0.7482 | likely_pathogenic | 0.7083 | pathogenic | -0.201 | Destabilizing | 0.975 | D | 0.662 | neutral | N | 0.446009199 | None | None | N |
| R/M | 0.8752 | likely_pathogenic | 0.8426 | pathogenic | -0.441 | Destabilizing | 0.999 | D | 0.741 | deleterious | None | None | None | None | N |
| R/N | 0.948 | likely_pathogenic | 0.939 | pathogenic | -0.317 | Destabilizing | 0.986 | D | 0.672 | neutral | None | None | None | None | N |
| R/P | 0.9738 | likely_pathogenic | 0.9732 | pathogenic | -0.445 | Destabilizing | 0.996 | D | 0.761 | deleterious | N | 0.497865821 | None | None | N |
| R/Q | 0.4054 | ambiguous | 0.3772 | ambiguous | -0.548 | Destabilizing | 0.997 | D | 0.674 | neutral | N | 0.433896042 | None | None | N |
| R/S | 0.9508 | likely_pathogenic | 0.9377 | pathogenic | -1.186 | Destabilizing | 0.953 | D | 0.707 | prob.neutral | None | None | None | None | N |
| R/T | 0.8793 | likely_pathogenic | 0.8392 | pathogenic | -0.888 | Destabilizing | 0.986 | D | 0.725 | prob.delet. | None | None | None | None | N |
| R/V | 0.8671 | likely_pathogenic | 0.8371 | pathogenic | -0.445 | Destabilizing | 0.993 | D | 0.757 | deleterious | None | None | None | None | N |
| R/W | 0.6983 | likely_pathogenic | 0.667 | pathogenic | -0.528 | Destabilizing | 0.999 | D | 0.729 | prob.delet. | None | None | None | None | N |
| R/Y | 0.8709 | likely_pathogenic | 0.8503 | pathogenic | -0.239 | Destabilizing | 0.998 | D | 0.757 | deleterious | 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.