Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 3074 | 9445;9446;9447 | chr2:178768099;178768098;178768097 | chr2:179632826;179632825;179632824 |
| N2AB | 3074 | 9445;9446;9447 | chr2:178768099;178768098;178768097 | chr2:179632826;179632825;179632824 |
| N2A | 3074 | 9445;9446;9447 | chr2:178768099;178768098;178768097 | chr2:179632826;179632825;179632824 |
| N2B | 3028 | 9307;9308;9309 | chr2:178768099;178768098;178768097 | chr2:179632826;179632825;179632824 |
| Novex-1 | 3028 | 9307;9308;9309 | chr2:178768099;178768098;178768097 | chr2:179632826;179632825;179632824 |
| Novex-2 | 3028 | 9307;9308;9309 | chr2:178768099;178768098;178768097 | chr2:179632826;179632825;179632824 |
| Novex-3 | 3074 | 9445;9446;9447 | chr2:178768099;178768098;178768097 | chr2:179632826;179632825;179632824 |
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/P | None | None | 0.998 | N | 0.474 | 0.492 | 0.533179623451 | gnomAD-4.0.0 | 6.84093E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.52232E-05 | None | 0 | 0 | 0 | 0 | 0 |
| R/Q | rs565052824  |
0.417 | 0.985 | N | 0.509 | 0.332 | 0.255270683199 | gnomAD-2.1.1 | 3.98E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.46E-05 | None | 0 | None | 0 | 0 | 0 |
| R/Q | rs565052824 |
0.417 | 0.985 | N | 0.509 | 0.332 | 0.255270683199 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 3.84615E-04 | None | 0 | 0 | 0 | 2.07297E-04 | 0 |
| R/Q | rs565052824 |
0.417 | 0.985 | N | 0.509 | 0.332 | 0.255270683199 | 1000 genomes | 3.99361E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 1E-03 | 0 | None | None | None | 1E-03 | None |
| R/Q | rs565052824 |
0.417 | 0.985 | N | 0.509 | 0.332 | 0.255270683199 | gnomAD-4.0.0 | 6.19551E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 8.9218E-05 | None | 0 | 0 | 2.54238E-06 | 3.29388E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.8116 | likely_pathogenic | 0.8486 | pathogenic | 0.011 | Stabilizing | 0.863 | D | 0.447 | neutral | None | None | None | None | N |
| R/C | 0.688 | likely_pathogenic | 0.7763 | pathogenic | -0.061 | Destabilizing | 0.999 | D | 0.497 | neutral | None | None | None | None | N |
| R/D | 0.9342 | likely_pathogenic | 0.9446 | pathogenic | -0.062 | Destabilizing | 0.969 | D | 0.467 | neutral | None | None | None | None | N |
| R/E | 0.7892 | likely_pathogenic | 0.8125 | pathogenic | 0.047 | Stabilizing | 0.863 | D | 0.453 | neutral | None | None | None | None | N |
| R/F | 0.8962 | likely_pathogenic | 0.9297 | pathogenic | 0.015 | Stabilizing | 0.997 | D | 0.477 | neutral | None | None | None | None | N |
| R/G | 0.7279 | likely_pathogenic | 0.7847 | pathogenic | -0.254 | Destabilizing | 0.983 | D | 0.477 | neutral | N | 0.503871543 | None | None | N |
| R/H | 0.3352 | likely_benign | 0.4082 | ambiguous | -0.889 | Destabilizing | 0.997 | D | 0.499 | neutral | None | None | None | None | N |
| R/I | 0.7171 | likely_pathogenic | 0.793 | pathogenic | 0.693 | Stabilizing | 0.997 | D | 0.486 | neutral | None | None | None | None | N |
| R/K | 0.2063 | likely_benign | 0.2622 | benign | -0.032 | Destabilizing | 0.028 | N | 0.149 | neutral | None | None | None | None | N |
| R/L | 0.6312 | likely_pathogenic | 0.6862 | pathogenic | 0.693 | Stabilizing | 0.983 | D | 0.477 | neutral | N | 0.503871543 | None | None | N |
| R/M | 0.6681 | likely_pathogenic | 0.7516 | pathogenic | 0.105 | Stabilizing | 0.997 | D | 0.47 | neutral | None | None | None | None | N |
| R/N | 0.8816 | likely_pathogenic | 0.9131 | pathogenic | 0.185 | Stabilizing | 0.969 | D | 0.475 | neutral | None | None | None | None | N |
| R/P | 0.8405 | likely_pathogenic | 0.8645 | pathogenic | 0.488 | Stabilizing | 0.998 | D | 0.474 | neutral | N | 0.501141303 | None | None | N |
| R/Q | 0.3235 | likely_benign | 0.3936 | ambiguous | 0.163 | Stabilizing | 0.985 | D | 0.509 | neutral | N | 0.502233658 | None | None | N |
| R/S | 0.8851 | likely_pathogenic | 0.9119 | pathogenic | -0.164 | Destabilizing | 0.939 | D | 0.473 | neutral | None | None | None | None | N |
| R/T | 0.6865 | likely_pathogenic | 0.7461 | pathogenic | 0.109 | Stabilizing | 0.969 | D | 0.475 | neutral | None | None | None | None | N |
| R/V | 0.734 | likely_pathogenic | 0.7988 | pathogenic | 0.488 | Stabilizing | 0.991 | D | 0.449 | neutral | None | None | None | None | N |
| R/W | 0.5323 | ambiguous | 0.5986 | pathogenic | 0.021 | Stabilizing | 0.999 | D | 0.566 | neutral | None | None | None | None | N |
| R/Y | 0.7714 | likely_pathogenic | 0.8313 | pathogenic | 0.405 | Stabilizing | 0.997 | D | 0.493 | neutral | 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.