Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16964 | 51115;51116;51117 | chr2:178611239;178611238;178611237 | chr2:179475966;179475965;179475964 |
| N2AB | 15323 | 46192;46193;46194 | chr2:178611239;178611238;178611237 | chr2:179475966;179475965;179475964 |
| N2A | 14396 | 43411;43412;43413 | chr2:178611239;178611238;178611237 | chr2:179475966;179475965;179475964 |
| N2B | 7899 | 23920;23921;23922 | chr2:178611239;178611238;178611237 | chr2:179475966;179475965;179475964 |
| Novex-1 | 8024 | 24295;24296;24297 | chr2:178611239;178611238;178611237 | chr2:179475966;179475965;179475964 |
| Novex-2 | 8091 | 24496;24497;24498 | chr2:178611239;178611238;178611237 | chr2:179475966;179475965;179475964 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/T | rs794729453  |
-2.163 | 0.891 | N | 0.459 | 0.426 | 0.822854388619 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.94E-06 | 0 |
| I/T | rs794729453 |
-2.163 | 0.891 | N | 0.459 | 0.426 | 0.822854388619 | gnomAD-4.0.0 | 8.21683E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 1.73853E-04 | 9.89855E-06 | 0 | 0 |
| I/V | rs1487972631 |
None | 0.267 | N | 0.303 | 0.037 | 0.508637063495 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.547 | ambiguous | 0.5095 | ambiguous | -2.091 | Highly Destabilizing | 0.688 | D | 0.461 | neutral | None | None | None | None | I |
| I/C | 0.7103 | likely_pathogenic | 0.6834 | pathogenic | -1.415 | Destabilizing | 0.998 | D | 0.455 | neutral | None | None | None | None | I |
| I/D | 0.8372 | likely_pathogenic | 0.7936 | pathogenic | -1.534 | Destabilizing | 0.991 | D | 0.597 | neutral | None | None | None | None | I |
| I/E | 0.7302 | likely_pathogenic | 0.6818 | pathogenic | -1.426 | Destabilizing | 0.991 | D | 0.582 | neutral | None | None | None | None | I |
| I/F | 0.2036 | likely_benign | 0.1759 | benign | -1.274 | Destabilizing | 0.934 | D | 0.433 | neutral | N | 0.510360144 | None | None | I |
| I/G | 0.8553 | likely_pathogenic | 0.8165 | pathogenic | -2.535 | Highly Destabilizing | 0.991 | D | 0.578 | neutral | None | None | None | None | I |
| I/H | 0.6008 | likely_pathogenic | 0.5331 | ambiguous | -1.747 | Destabilizing | 0.998 | D | 0.578 | neutral | None | None | None | None | I |
| I/K | 0.4734 | ambiguous | 0.404 | ambiguous | -1.569 | Destabilizing | 0.974 | D | 0.569 | neutral | None | None | None | None | I |
| I/L | 0.1184 | likely_benign | 0.1166 | benign | -0.883 | Destabilizing | 0.002 | N | 0.105 | neutral | N | 0.476128292 | None | None | I |
| I/M | 0.1048 | likely_benign | 0.1022 | benign | -0.749 | Destabilizing | 0.934 | D | 0.466 | neutral | N | 0.51420548 | None | None | I |
| I/N | 0.4408 | ambiguous | 0.3913 | ambiguous | -1.556 | Destabilizing | 0.989 | D | 0.613 | neutral | D | 0.60400772 | None | None | I |
| I/P | 0.9761 | likely_pathogenic | 0.9664 | pathogenic | -1.258 | Destabilizing | 0.991 | D | 0.611 | neutral | None | None | None | None | I |
| I/Q | 0.568 | likely_pathogenic | 0.5115 | ambiguous | -1.575 | Destabilizing | 0.991 | D | 0.604 | neutral | None | None | None | None | I |
| I/R | 0.4166 | ambiguous | 0.3337 | benign | -1.103 | Destabilizing | 0.974 | D | 0.599 | neutral | None | None | None | None | I |
| I/S | 0.539 | ambiguous | 0.4874 | ambiguous | -2.291 | Highly Destabilizing | 0.966 | D | 0.516 | neutral | D | 0.535552409 | None | None | I |
| I/T | 0.3516 | ambiguous | 0.3163 | benign | -2.042 | Highly Destabilizing | 0.891 | D | 0.459 | neutral | N | 0.514008381 | None | None | I |
| I/V | 0.091 | likely_benign | 0.0902 | benign | -1.258 | Destabilizing | 0.267 | N | 0.303 | neutral | N | 0.475344594 | None | None | I |
| I/W | 0.8016 | likely_pathogenic | 0.7703 | pathogenic | -1.443 | Destabilizing | 0.998 | D | 0.608 | neutral | None | None | None | None | I |
| I/Y | 0.5372 | ambiguous | 0.4911 | ambiguous | -1.207 | Destabilizing | 0.991 | D | 0.475 | neutral | None | None | 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.