Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20976 | 63151;63152;63153 | chr2:178588799;178588798;178588797 | chr2:179453526;179453525;179453524 |
| N2AB | 19335 | 58228;58229;58230 | chr2:178588799;178588798;178588797 | chr2:179453526;179453525;179453524 |
| N2A | 18408 | 55447;55448;55449 | chr2:178588799;178588798;178588797 | chr2:179453526;179453525;179453524 |
| N2B | 11911 | 35956;35957;35958 | chr2:178588799;178588798;178588797 | chr2:179453526;179453525;179453524 |
| Novex-1 | 12036 | 36331;36332;36333 | chr2:178588799;178588798;178588797 | chr2:179453526;179453525;179453524 |
| Novex-2 | 12103 | 36532;36533;36534 | chr2:178588799;178588798;178588797 | chr2:179453526;179453525;179453524 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/R | rs1225927295  |
-0.557 | 0.971 | N | 0.525 | 0.238 | 0.279776271856 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.88E-06 | 0 |
| S/R | rs1225927295 |
-0.557 | 0.971 | N | 0.525 | 0.238 | 0.279776271856 | gnomAD-4.0.0 | 3.42197E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.49805E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.1188 | likely_benign | 0.1366 | benign | -0.46 | Destabilizing | 0.559 | D | 0.421 | neutral | None | None | None | None | N |
| S/C | 0.1287 | likely_benign | 0.1327 | benign | -0.507 | Destabilizing | 0.997 | D | 0.511 | neutral | N | 0.472386424 | None | None | N |
| S/D | 0.6566 | likely_pathogenic | 0.5266 | ambiguous | -1.236 | Destabilizing | 0.86 | D | 0.5 | neutral | None | None | None | None | N |
| S/E | 0.8329 | likely_pathogenic | 0.7544 | pathogenic | -1.201 | Destabilizing | 0.926 | D | 0.491 | neutral | None | None | None | None | N |
| S/F | 0.533 | ambiguous | 0.4915 | ambiguous | -0.494 | Destabilizing | 0.993 | D | 0.577 | neutral | None | None | None | None | N |
| S/G | 0.0638 | likely_benign | 0.0678 | benign | -0.749 | Destabilizing | 0.006 | N | 0.187 | neutral | N | 0.412930204 | None | None | N |
| S/H | 0.6071 | likely_pathogenic | 0.5468 | ambiguous | -1.336 | Destabilizing | 0.998 | D | 0.501 | neutral | None | None | None | None | N |
| S/I | 0.5438 | ambiguous | 0.5007 | ambiguous | 0.207 | Stabilizing | 0.971 | D | 0.567 | neutral | D | 0.524063554 | None | None | N |
| S/K | 0.8872 | likely_pathogenic | 0.8211 | pathogenic | -0.941 | Destabilizing | 0.86 | D | 0.496 | neutral | None | None | None | None | N |
| S/L | 0.2162 | likely_benign | 0.2055 | benign | 0.207 | Stabilizing | 0.978 | D | 0.488 | neutral | None | None | None | None | N |
| S/M | 0.3315 | likely_benign | 0.3237 | benign | 0.452 | Stabilizing | 0.998 | D | 0.497 | neutral | None | None | None | None | N |
| S/N | 0.1988 | likely_benign | 0.1712 | benign | -1.122 | Destabilizing | 0.822 | D | 0.521 | neutral | N | 0.453142031 | None | None | N |
| S/P | 0.9524 | likely_pathogenic | 0.9326 | pathogenic | 0.02 | Stabilizing | 0.993 | D | 0.508 | neutral | None | None | None | None | N |
| S/Q | 0.7311 | likely_pathogenic | 0.6756 | pathogenic | -1.211 | Destabilizing | 0.993 | D | 0.517 | neutral | None | None | None | None | N |
| S/R | 0.84 | likely_pathogenic | 0.7611 | pathogenic | -0.873 | Destabilizing | 0.971 | D | 0.525 | neutral | N | 0.432806831 | None | None | N |
| S/T | 0.0879 | likely_benign | 0.0853 | benign | -0.909 | Destabilizing | 0.904 | D | 0.464 | neutral | N | 0.369907359 | None | None | N |
| S/V | 0.4709 | ambiguous | 0.4488 | ambiguous | 0.02 | Stabilizing | 0.978 | D | 0.529 | neutral | None | None | None | None | N |
| S/W | 0.6795 | likely_pathogenic | 0.6139 | pathogenic | -0.635 | Destabilizing | 0.998 | D | 0.639 | neutral | None | None | None | None | N |
| S/Y | 0.4838 | ambiguous | 0.4336 | ambiguous | -0.315 | Destabilizing | 0.993 | D | 0.58 | 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.