Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 139 | 640;641;642 | chr2:178800563;178800562;178800561 | chr2:179665290;179665289;179665288 |
| N2AB | 139 | 640;641;642 | chr2:178800563;178800562;178800561 | chr2:179665290;179665289;179665288 |
| N2A | 139 | 640;641;642 | chr2:178800563;178800562;178800561 | chr2:179665290;179665289;179665288 |
| N2B | 139 | 640;641;642 | chr2:178800563;178800562;178800561 | chr2:179665290;179665289;179665288 |
| Novex-1 | 139 | 640;641;642 | chr2:178800563;178800562;178800561 | chr2:179665290;179665289;179665288 |
| Novex-2 | 139 | 640;641;642 | chr2:178800563;178800562;178800561 | chr2:179665290;179665289;179665288 |
| Novex-3 | 139 | 640;641;642 | chr2:178800563;178800562;178800561 | chr2:179665290;179665289;179665288 |
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/Q | rs780003580  |
-0.997 | 0.999 | D | 0.52 | 0.603 | 0.388010793773 | gnomAD-2.1.1 | 2.39E-05 | None | None | None | -0.66(TCAP) | N | None | 0 | 0 | None | 0 | 0 | None | 9.8E-05 | None | 0 | 2.64E-05 | 0 |
| R/Q | rs780003580 |
-0.997 | 0.999 | D | 0.52 | 0.603 | 0.388010793773 | gnomAD-4.0.0 | 1.36814E-05 | None | None | None | -0.66(TCAP) | N | None | 0 | 2.23604E-05 | None | 0 | 2.51953E-05 | None | 0 | 0 | 1.43888E-05 | 2.31863E-05 | 0 |
| R/W | rs752970602 |
-0.876 | 0.316 | D | 0.551 | 0.558 | 0.436780212511 | gnomAD-2.1.1 | 8.49E-05 | None | None | None | -1.311(TCAP) | N | None | 0 | 8.47E-05 | None | 0 | 0 | None | 0 | None | 0 | 1.62745E-04 | 0 |
| R/W | rs752970602 |
-0.876 | 0.316 | D | 0.551 | 0.558 | 0.436780212511 | gnomAD-3.1.2 | 4.6E-05 | None | None | None | -1.311(TCAP) | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 7.35E-05 | 0 | 0 |
| R/W | rs752970602 |
-0.876 | 0.316 | D | 0.551 | 0.558 | 0.436780212511 | gnomAD-4.0.0 | 1.06568E-04 | None | None | None | -1.311(TCAP) | N | None | 2.6693E-05 | 8.33417E-05 | None | 0 | 0 | None | 0 | 0 | 1.34745E-04 | 1.09786E-05 | 8.0023E-05 |
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 | 0.9828 | likely_pathogenic | 0.9789 | pathogenic | -1.819 | Destabilizing | 0.91 | D | 0.536 | neutral | None | None | None | -1.178(TCAP) | N |
| R/C | 0.8719 | likely_pathogenic | 0.874 | pathogenic | -1.723 | Destabilizing | 0.999 | D | 0.727 | prob.delet. | None | None | None | -1.327(TCAP) | N |
| R/D | 0.996 | likely_pathogenic | 0.9946 | pathogenic | -0.451 | Destabilizing | 0.995 | D | 0.693 | prob.neutral | None | None | None | -0.263(TCAP) | N |
| R/E | 0.9535 | likely_pathogenic | 0.9441 | pathogenic | -0.272 | Destabilizing | 0.86 | D | 0.527 | neutral | None | None | None | -0.328(TCAP) | N |
| R/F | 0.9894 | likely_pathogenic | 0.9887 | pathogenic | -1.518 | Destabilizing | 0.876 | D | 0.731 | prob.delet. | None | None | None | -1.275(TCAP) | N |
| R/G | 0.9782 | likely_pathogenic | 0.9716 | pathogenic | -2.154 | Highly Destabilizing | 0.951 | D | 0.629 | neutral | D | 0.594210514 | None | -1.114(TCAP) | N |
| R/H | 0.576 | likely_pathogenic | 0.5416 | ambiguous | -2.288 | Highly Destabilizing | 0.989 | D | 0.568 | neutral | None | None | None | -0.694(TCAP) | N |
| R/I | 0.9654 | likely_pathogenic | 0.9572 | pathogenic | -0.872 | Destabilizing | 0.968 | D | 0.734 | prob.delet. | None | None | None | -1.363(TCAP) | N |
| R/K | 0.4129 | ambiguous | 0.4108 | ambiguous | -1.289 | Destabilizing | 0.71 | D | 0.522 | neutral | None | None | None | -0.374(TCAP) | N |
| R/L | 0.9175 | likely_pathogenic | 0.9161 | pathogenic | -0.872 | Destabilizing | 0.801 | D | 0.629 | neutral | D | 0.522851451 | None | -1.363(TCAP) | N |
| R/M | 0.9688 | likely_pathogenic | 0.9644 | pathogenic | -1.13 | Destabilizing | 0.997 | D | 0.673 | neutral | None | None | None | -1.255(TCAP) | N |
| R/N | 0.9926 | likely_pathogenic | 0.9902 | pathogenic | -1.008 | Destabilizing | 0.995 | D | 0.521 | neutral | None | None | None | -0.653(TCAP) | N |
| R/P | 0.9984 | likely_pathogenic | 0.9982 | pathogenic | -1.172 | Destabilizing | 0.998 | D | 0.703 | prob.neutral | D | 0.615176054 | None | -1.303(TCAP) | N |
| R/Q | 0.5272 | ambiguous | 0.4956 | ambiguous | -1.1 | Destabilizing | 0.999 | D | 0.52 | neutral | D | 0.575867632 | None | -0.66(TCAP) | N |
| R/S | 0.9876 | likely_pathogenic | 0.9826 | pathogenic | -2.056 | Highly Destabilizing | 0.986 | D | 0.587 | neutral | None | None | None | -0.411(TCAP) | N |
| R/T | 0.981 | likely_pathogenic | 0.9729 | pathogenic | -1.656 | Destabilizing | 0.986 | D | 0.592 | neutral | None | None | None | -0.516(TCAP) | N |
| R/V | 0.9711 | likely_pathogenic | 0.9656 | pathogenic | -1.172 | Destabilizing | 0.956 | D | 0.712 | prob.delet. | None | None | None | -1.303(TCAP) | N |
| R/W | 0.8975 | likely_pathogenic | 0.8872 | pathogenic | -0.996 | Destabilizing | 0.316 | N | 0.551 | neutral | D | 0.724375216 | None | -1.311(TCAP) | N |
| R/Y | 0.9683 | likely_pathogenic | 0.9643 | pathogenic | -0.816 | Destabilizing | 0.876 | D | 0.692 | prob.neutral | None | None | None | -1.35(TCAP) | 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.