Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27267 | 82024;82025;82026 | chr2:178564333;178564332;178564331 | chr2:179429060;179429059;179429058 |
| N2AB | 25626 | 77101;77102;77103 | chr2:178564333;178564332;178564331 | chr2:179429060;179429059;179429058 |
| N2A | 24699 | 74320;74321;74322 | chr2:178564333;178564332;178564331 | chr2:179429060;179429059;179429058 |
| N2B | 18202 | 54829;54830;54831 | chr2:178564333;178564332;178564331 | chr2:179429060;179429059;179429058 |
| Novex-1 | 18327 | 55204;55205;55206 | chr2:178564333;178564332;178564331 | chr2:179429060;179429059;179429058 |
| Novex-2 | 18394 | 55405;55406;55407 | chr2:178564333;178564332;178564331 | chr2:179429060;179429059;179429058 |
| 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/K | rs975294048  |
None | 0.029 | N | 0.113 | 0.169 | 0.12205267543 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| R/K | rs975294048 |
None | 0.029 | N | 0.113 | 0.169 | 0.12205267543 | gnomAD-4.0.0 | 1.31499E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.94109E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.628 | likely_pathogenic | 0.5652 | pathogenic | -0.731 | Destabilizing | 0.745 | D | 0.422 | neutral | None | None | None | None | N |
| R/C | 0.2825 | likely_benign | 0.2469 | benign | -0.576 | Destabilizing | 0.998 | D | 0.564 | neutral | None | None | None | None | N |
| R/D | 0.9227 | likely_pathogenic | 0.9005 | pathogenic | -0.193 | Destabilizing | 0.876 | D | 0.484 | neutral | None | None | None | None | N |
| R/E | 0.61 | likely_pathogenic | 0.5416 | ambiguous | -0.099 | Destabilizing | 0.594 | D | 0.365 | neutral | None | None | None | None | N |
| R/F | 0.7655 | likely_pathogenic | 0.7177 | pathogenic | -0.747 | Destabilizing | 0.994 | D | 0.52 | neutral | None | None | None | None | N |
| R/G | 0.5699 | likely_pathogenic | 0.497 | ambiguous | -1.011 | Destabilizing | 0.915 | D | 0.455 | neutral | N | 0.474858524 | None | None | N |
| R/H | 0.1839 | likely_benign | 0.1586 | benign | -1.359 | Destabilizing | 0.981 | D | 0.3 | neutral | None | None | None | None | N |
| R/I | 0.4469 | ambiguous | 0.3907 | ambiguous | 0.012 | Stabilizing | 0.991 | D | 0.603 | neutral | N | 0.477282753 | None | None | N |
| R/K | 0.0891 | likely_benign | 0.0814 | benign | -0.784 | Destabilizing | 0.029 | N | 0.113 | neutral | N | 0.355071192 | None | None | N |
| R/L | 0.4399 | ambiguous | 0.3968 | ambiguous | 0.012 | Stabilizing | 0.876 | D | 0.455 | neutral | None | None | None | None | N |
| R/M | 0.446 | ambiguous | 0.3852 | ambiguous | -0.145 | Destabilizing | 0.994 | D | 0.369 | neutral | None | None | None | None | N |
| R/N | 0.8276 | likely_pathogenic | 0.7863 | pathogenic | -0.161 | Destabilizing | 0.935 | D | 0.352 | neutral | None | None | None | None | N |
| R/P | 0.9791 | likely_pathogenic | 0.9741 | pathogenic | -0.215 | Destabilizing | 0.994 | D | 0.523 | neutral | None | None | None | None | N |
| R/Q | 0.1615 | likely_benign | 0.1383 | benign | -0.414 | Destabilizing | 0.216 | N | 0.197 | neutral | None | None | None | None | N |
| R/S | 0.7468 | likely_pathogenic | 0.6804 | pathogenic | -0.875 | Destabilizing | 0.842 | D | 0.429 | neutral | N | 0.514107558 | None | None | N |
| R/T | 0.4343 | ambiguous | 0.3651 | ambiguous | -0.618 | Destabilizing | 0.915 | D | 0.377 | neutral | N | 0.447557279 | None | None | N |
| R/V | 0.499 | ambiguous | 0.4462 | ambiguous | -0.215 | Destabilizing | 0.935 | D | 0.558 | neutral | None | None | None | None | N |
| R/W | 0.4003 | ambiguous | 0.3369 | benign | -0.454 | Destabilizing | 0.998 | D | 0.617 | neutral | None | None | None | None | N |
| R/Y | 0.6599 | likely_pathogenic | 0.6131 | pathogenic | -0.131 | Destabilizing | 0.994 | D | 0.553 | 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.