Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2979 | 9160;9161;9162 | chr2:178768901;178768900;178768899 | chr2:179633628;179633627;179633626 |
| N2AB | 2979 | 9160;9161;9162 | chr2:178768901;178768900;178768899 | chr2:179633628;179633627;179633626 |
| N2A | 2979 | 9160;9161;9162 | chr2:178768901;178768900;178768899 | chr2:179633628;179633627;179633626 |
| N2B | 2933 | 9022;9023;9024 | chr2:178768901;178768900;178768899 | chr2:179633628;179633627;179633626 |
| Novex-1 | 2933 | 9022;9023;9024 | chr2:178768901;178768900;178768899 | chr2:179633628;179633627;179633626 |
| Novex-2 | 2933 | 9022;9023;9024 | chr2:178768901;178768900;178768899 | chr2:179633628;179633627;179633626 |
| Novex-3 | 2979 | 9160;9161;9162 | chr2:178768901;178768900;178768899 | chr2:179633628;179633627;179633626 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/S | rs765890815  |
0.183 | 0.996 | N | 0.418 | 0.364 | 0.290590437066 | gnomAD-2.1.1 | 7.97E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 6.53E-05 | None | 0 | 0 | 0 |
| N/S | rs765890815 |
0.183 | 0.996 | N | 0.418 | 0.364 | 0.290590437066 | gnomAD-4.0.0 | 3.18176E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.86549E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/A | 0.3945 | ambiguous | 0.4232 | ambiguous | -0.508 | Destabilizing | 0.997 | D | 0.563 | neutral | None | None | None | None | N |
| N/C | 0.4677 | ambiguous | 0.5145 | ambiguous | 0.149 | Stabilizing | 1.0 | D | 0.709 | prob.delet. | None | None | None | None | N |
| N/D | 0.313 | likely_benign | 0.3023 | benign | 0.281 | Stabilizing | 0.998 | D | 0.492 | neutral | N | 0.498178122 | None | None | N |
| N/E | 0.6245 | likely_pathogenic | 0.6481 | pathogenic | 0.315 | Stabilizing | 0.997 | D | 0.504 | neutral | None | None | None | None | N |
| N/F | 0.721 | likely_pathogenic | 0.7377 | pathogenic | -0.582 | Destabilizing | 1.0 | D | 0.707 | prob.neutral | None | None | None | None | N |
| N/G | 0.6163 | likely_pathogenic | 0.614 | pathogenic | -0.762 | Destabilizing | 0.998 | D | 0.433 | neutral | None | None | None | None | N |
| N/H | 0.1233 | likely_benign | 0.1318 | benign | -0.531 | Destabilizing | 1.0 | D | 0.637 | neutral | N | 0.473029838 | None | None | N |
| N/I | 0.3264 | likely_benign | 0.3469 | ambiguous | 0.095 | Stabilizing | 1.0 | D | 0.737 | prob.delet. | N | 0.506094291 | None | None | N |
| N/K | 0.3963 | ambiguous | 0.4769 | ambiguous | 0.064 | Stabilizing | 0.893 | D | 0.303 | neutral | N | 0.458790389 | None | None | N |
| N/L | 0.3602 | ambiguous | 0.3706 | ambiguous | 0.095 | Stabilizing | 1.0 | D | 0.665 | neutral | None | None | None | None | N |
| N/M | 0.4664 | ambiguous | 0.5011 | ambiguous | 0.244 | Stabilizing | 1.0 | D | 0.641 | neutral | None | None | None | None | N |
| N/P | 0.7827 | likely_pathogenic | 0.7816 | pathogenic | -0.077 | Destabilizing | 1.0 | D | 0.692 | prob.neutral | None | None | None | None | N |
| N/Q | 0.481 | ambiguous | 0.523 | ambiguous | -0.41 | Destabilizing | 0.999 | D | 0.649 | neutral | None | None | None | None | N |
| N/R | 0.4344 | ambiguous | 0.4875 | ambiguous | 0.077 | Stabilizing | 0.998 | D | 0.592 | neutral | None | None | None | None | N |
| N/S | 0.114 | likely_benign | 0.1092 | benign | -0.406 | Destabilizing | 0.996 | D | 0.418 | neutral | N | 0.497092799 | None | None | N |
| N/T | 0.1805 | likely_benign | 0.1952 | benign | -0.194 | Destabilizing | 0.998 | D | 0.532 | neutral | N | 0.455601313 | None | None | N |
| N/V | 0.3316 | likely_benign | 0.3619 | ambiguous | -0.077 | Destabilizing | 1.0 | D | 0.723 | prob.delet. | None | None | None | None | N |
| N/W | 0.8882 | likely_pathogenic | 0.9022 | pathogenic | -0.461 | Destabilizing | 1.0 | D | 0.713 | prob.delet. | None | None | None | None | N |
| N/Y | 0.2602 | likely_benign | 0.2801 | benign | -0.215 | Destabilizing | 1.0 | D | 0.698 | prob.neutral | N | 0.510426929 | 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.