Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 13808 | 41647;41648;41649 | chr2:178636149;178636148;178636147 | chr2:179500876;179500875;179500874 |
| N2AB | 12167 | 36724;36725;36726 | chr2:178636149;178636148;178636147 | chr2:179500876;179500875;179500874 |
| N2A | 11240 | 33943;33944;33945 | chr2:178636149;178636148;178636147 | chr2:179500876;179500875;179500874 |
| N2B | 4743 | 14452;14453;14454 | chr2:178636149;178636148;178636147 | chr2:179500876;179500875;179500874 |
| Novex-1 | 4868 | 14827;14828;14829 | chr2:178636149;178636148;178636147 | chr2:179500876;179500875;179500874 |
| Novex-2 | 4935 | 15028;15029;15030 | chr2:178636149;178636148;178636147 | chr2:179500876;179500875;179500874 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/C | rs375947044  |
-0.216 | 1.0 | N | 0.817 | 0.197 | None | gnomAD-2.1.1 | 1.61E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 6.55E-05 | None | 0 | 1.78E-05 | 0 |
| R/C | rs375947044 |
-0.216 | 1.0 | N | 0.817 | 0.197 | None | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 4.15628E-04 | 0 |
| R/C | rs375947044 |
-0.216 | 1.0 | N | 0.817 | 0.197 | None | 1000 genomes | 3.99361E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 2E-03 | None |
| R/C | rs375947044 |
-0.216 | 1.0 | N | 0.817 | 0.197 | None | gnomAD-4.0.0 | 9.29985E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.47872E-06 | 5.49318E-05 | 0 |
| R/H | rs764850788 |
-0.655 | 1.0 | N | 0.645 | 0.319 | 0.253726318573 | gnomAD-2.1.1 | 2.02E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.69338E-04 | None | 0 | None | 0 | 1.78E-05 | 0 |
| R/H | rs764850788 |
-0.655 | 1.0 | N | 0.645 | 0.319 | 0.253726318573 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/H | rs764850788 |
-0.655 | 1.0 | N | 0.645 | 0.319 | 0.253726318573 | gnomAD-4.0.0 | 5.57979E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 4.48069E-05 | None | 0 | 0 | 5.93487E-06 | 0 | 0 |
| R/S | rs375947044 |
-0.22 | 0.996 | N | 0.586 | 0.175 | 0.221734844693 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| R/S | rs375947044 |
-0.22 | 0.996 | N | 0.586 | 0.175 | 0.221734844693 | gnomAD-4.0.0 | 6.84539E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.1599E-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 | 0.7451 | likely_pathogenic | 0.7233 | pathogenic | -0.168 | Destabilizing | 0.992 | D | 0.517 | neutral | None | None | None | None | N |
| R/C | 0.4432 | ambiguous | 0.4319 | ambiguous | -0.225 | Destabilizing | 1.0 | D | 0.817 | deleterious | N | 0.311130877 | None | None | N |
| R/D | 0.9265 | likely_pathogenic | 0.9164 | pathogenic | 0.01 | Stabilizing | 0.999 | D | 0.691 | prob.delet. | None | None | None | None | N |
| R/E | 0.6735 | likely_pathogenic | 0.6505 | pathogenic | 0.149 | Stabilizing | 0.992 | D | 0.492 | neutral | None | None | None | None | N |
| R/F | 0.9206 | likely_pathogenic | 0.9079 | pathogenic | 0.004 | Stabilizing | 1.0 | D | 0.771 | deleterious | None | None | None | None | N |
| R/G | 0.6018 | likely_pathogenic | 0.5685 | pathogenic | -0.474 | Destabilizing | 0.998 | D | 0.455 | neutral | N | 0.347932188 | None | None | N |
| R/H | 0.333 | likely_benign | 0.3175 | benign | -1.027 | Destabilizing | 1.0 | D | 0.645 | neutral | N | 0.331061515 | None | None | N |
| R/I | 0.6765 | likely_pathogenic | 0.6406 | pathogenic | 0.641 | Stabilizing | 1.0 | D | 0.787 | deleterious | None | None | None | None | N |
| R/K | 0.2062 | likely_benign | 0.204 | benign | -0.122 | Destabilizing | 0.611 | D | 0.352 | neutral | None | None | None | None | N |
| R/L | 0.6449 | likely_pathogenic | 0.614 | pathogenic | 0.641 | Stabilizing | 0.998 | D | 0.455 | neutral | N | 0.342769569 | None | None | N |
| R/M | 0.6587 | likely_pathogenic | 0.6201 | pathogenic | 0.027 | Stabilizing | 1.0 | D | 0.61 | neutral | None | None | None | None | N |
| R/N | 0.8847 | likely_pathogenic | 0.87 | pathogenic | 0.096 | Stabilizing | 0.999 | D | 0.587 | neutral | None | None | None | None | N |
| R/P | 0.9465 | likely_pathogenic | 0.9325 | pathogenic | 0.394 | Stabilizing | 1.0 | D | 0.768 | deleterious | N | 0.319543158 | None | None | N |
| R/Q | 0.2198 | likely_benign | 0.2106 | benign | 0.098 | Stabilizing | 0.998 | D | 0.613 | neutral | None | None | None | None | N |
| R/S | 0.839 | likely_pathogenic | 0.82 | pathogenic | -0.377 | Destabilizing | 0.996 | D | 0.586 | neutral | N | 0.340264689 | None | None | N |
| R/T | 0.6309 | likely_pathogenic | 0.5954 | pathogenic | -0.051 | Destabilizing | 0.999 | D | 0.531 | neutral | None | None | None | None | N |
| R/V | 0.717 | likely_pathogenic | 0.6955 | pathogenic | 0.394 | Stabilizing | 0.999 | D | 0.764 | deleterious | None | None | None | None | N |
| R/W | 0.59 | likely_pathogenic | 0.536 | ambiguous | 0.119 | Stabilizing | 1.0 | D | 0.833 | deleterious | None | None | None | None | N |
| R/Y | 0.8111 | likely_pathogenic | 0.7862 | pathogenic | 0.467 | Stabilizing | 1.0 | D | 0.769 | 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.