Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19707 | 59344;59345;59346 | chr2:178593000;178592999;178592998 | chr2:179457727;179457726;179457725 |
| N2AB | 18066 | 54421;54422;54423 | chr2:178593000;178592999;178592998 | chr2:179457727;179457726;179457725 |
| N2A | 17139 | 51640;51641;51642 | chr2:178593000;178592999;178592998 | chr2:179457727;179457726;179457725 |
| N2B | 10642 | 32149;32150;32151 | chr2:178593000;178592999;178592998 | chr2:179457727;179457726;179457725 |
| Novex-1 | 10767 | 32524;32525;32526 | chr2:178593000;178592999;178592998 | chr2:179457727;179457726;179457725 |
| Novex-2 | 10834 | 32725;32726;32727 | chr2:178593000;178592999;178592998 | chr2:179457727;179457726;179457725 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/G | None | None | 0.959 | N | 0.413 | 0.403 | 0.406945738958 | gnomAD-4.0.0 | 1.59189E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.0248E-05 |
| D/H | None | None | 0.999 | N | 0.549 | 0.413 | 0.468753983522 | gnomAD-4.0.0 | 1.20034E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.31252E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.5879 | likely_pathogenic | 0.5737 | pathogenic | -0.423 | Destabilizing | 0.826 | D | 0.503 | neutral | N | 0.490095377 | None | None | I |
| D/C | 0.8597 | likely_pathogenic | 0.8519 | pathogenic | 0.091 | Stabilizing | 0.1 | N | 0.417 | neutral | None | None | None | None | I |
| D/E | 0.5419 | ambiguous | 0.5394 | ambiguous | -0.558 | Destabilizing | 0.959 | D | 0.377 | neutral | N | 0.484966816 | None | None | I |
| D/F | 0.9066 | likely_pathogenic | 0.9151 | pathogenic | -0.562 | Destabilizing | 0.997 | D | 0.625 | neutral | None | None | None | None | I |
| D/G | 0.603 | likely_pathogenic | 0.5504 | ambiguous | -0.666 | Destabilizing | 0.959 | D | 0.413 | neutral | N | 0.507580976 | None | None | I |
| D/H | 0.6709 | likely_pathogenic | 0.6317 | pathogenic | -0.856 | Destabilizing | 0.999 | D | 0.549 | neutral | N | 0.508960101 | None | None | I |
| D/I | 0.7994 | likely_pathogenic | 0.8195 | pathogenic | 0.183 | Stabilizing | 0.982 | D | 0.589 | neutral | None | None | None | None | I |
| D/K | 0.8443 | likely_pathogenic | 0.8233 | pathogenic | 0.095 | Stabilizing | 0.969 | D | 0.469 | neutral | None | None | None | None | I |
| D/L | 0.8138 | likely_pathogenic | 0.8251 | pathogenic | 0.183 | Stabilizing | 0.939 | D | 0.565 | neutral | None | None | None | None | I |
| D/M | 0.9105 | likely_pathogenic | 0.9168 | pathogenic | 0.622 | Stabilizing | 0.999 | D | 0.615 | neutral | None | None | None | None | I |
| D/N | 0.148 | likely_benign | 0.1476 | benign | -0.18 | Destabilizing | 0.959 | D | 0.499 | neutral | N | 0.470105018 | None | None | I |
| D/P | 0.8948 | likely_pathogenic | 0.8892 | pathogenic | 0.005 | Stabilizing | 0.997 | D | 0.531 | neutral | None | None | None | None | I |
| D/Q | 0.7919 | likely_pathogenic | 0.7616 | pathogenic | -0.135 | Destabilizing | 0.997 | D | 0.522 | neutral | None | None | None | None | I |
| D/R | 0.8482 | likely_pathogenic | 0.8153 | pathogenic | 0.034 | Stabilizing | 0.991 | D | 0.611 | neutral | None | None | None | None | I |
| D/S | 0.3177 | likely_benign | 0.2854 | benign | -0.324 | Destabilizing | 0.884 | D | 0.393 | neutral | None | None | None | None | I |
| D/T | 0.5665 | likely_pathogenic | 0.542 | ambiguous | -0.128 | Destabilizing | 0.079 | N | 0.177 | neutral | None | None | None | None | I |
| D/V | 0.6622 | likely_pathogenic | 0.679 | pathogenic | 0.005 | Stabilizing | 0.92 | D | 0.57 | neutral | N | 0.501046836 | None | None | I |
| D/W | 0.977 | likely_pathogenic | 0.9758 | pathogenic | -0.494 | Destabilizing | 0.999 | D | 0.673 | neutral | None | None | None | None | I |
| D/Y | 0.6106 | likely_pathogenic | 0.5845 | pathogenic | -0.34 | Destabilizing | 0.996 | D | 0.628 | neutral | D | 0.541814476 | None | None | I |
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.