Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2970 | 9133;9134;9135 | chr2:178768928;178768927;178768926 | chr2:179633655;179633654;179633653 |
| N2AB | 2970 | 9133;9134;9135 | chr2:178768928;178768927;178768926 | chr2:179633655;179633654;179633653 |
| N2A | 2970 | 9133;9134;9135 | chr2:178768928;178768927;178768926 | chr2:179633655;179633654;179633653 |
| N2B | 2924 | 8995;8996;8997 | chr2:178768928;178768927;178768926 | chr2:179633655;179633654;179633653 |
| Novex-1 | 2924 | 8995;8996;8997 | chr2:178768928;178768927;178768926 | chr2:179633655;179633654;179633653 |
| Novex-2 | 2924 | 8995;8996;8997 | chr2:178768928;178768927;178768926 | chr2:179633655;179633654;179633653 |
| Novex-3 | 2970 | 9133;9134;9135 | chr2:178768928;178768927;178768926 | chr2:179633655;179633654;179633653 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/I | None | None | 0.019 | N | 0.265 | 0.133 | 0.414281671643 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| M/T | None | None | 0.175 | N | 0.38 | 0.33 | None | gnomAD-4.0.0 | 1.59137E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85664E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.3524 | ambiguous | 0.4455 | ambiguous | -0.83 | Destabilizing | 0.104 | N | 0.396 | neutral | None | None | None | None | N |
| M/C | 0.7452 | likely_pathogenic | 0.8137 | pathogenic | -0.794 | Destabilizing | 0.859 | D | 0.383 | neutral | None | None | None | None | N |
| M/D | 0.8164 | likely_pathogenic | 0.876 | pathogenic | -0.027 | Destabilizing | 0.859 | D | 0.413 | neutral | None | None | None | None | N |
| M/E | 0.4574 | ambiguous | 0.5223 | ambiguous | -0.039 | Destabilizing | 0.364 | N | 0.413 | neutral | None | None | None | None | N |
| M/F | 0.4268 | ambiguous | 0.5085 | ambiguous | -0.191 | Destabilizing | 0.124 | N | 0.252 | neutral | None | None | None | None | N |
| M/G | 0.6881 | likely_pathogenic | 0.7713 | pathogenic | -1.056 | Destabilizing | 0.364 | N | 0.424 | neutral | None | None | None | None | N |
| M/H | 0.4607 | ambiguous | 0.5401 | ambiguous | -0.098 | Destabilizing | 0.958 | D | 0.369 | neutral | None | None | None | None | N |
| M/I | 0.3066 | likely_benign | 0.4249 | ambiguous | -0.301 | Destabilizing | 0.019 | N | 0.265 | neutral | N | 0.413924349 | None | None | N |
| M/K | 0.1627 | likely_benign | 0.1978 | benign | -0.02 | Destabilizing | 0.301 | N | 0.378 | neutral | N | 0.433170668 | None | None | N |
| M/L | 0.0957 | likely_benign | 0.1156 | benign | -0.301 | Destabilizing | None | N | 0.129 | neutral | N | 0.381452771 | None | None | N |
| M/N | 0.455 | ambiguous | 0.567 | pathogenic | 0.037 | Stabilizing | 0.859 | D | 0.417 | neutral | None | None | None | None | N |
| M/P | 0.9394 | likely_pathogenic | 0.9665 | pathogenic | -0.45 | Destabilizing | 0.859 | D | 0.419 | neutral | None | None | None | None | N |
| M/Q | 0.2428 | likely_benign | 0.2621 | benign | -0.072 | Destabilizing | 0.859 | D | 0.344 | neutral | None | None | None | None | N |
| M/R | 0.21 | likely_benign | 0.232 | benign | 0.513 | Stabilizing | 0.301 | N | 0.42 | neutral | N | 0.484239506 | None | None | N |
| M/S | 0.4173 | ambiguous | 0.5119 | ambiguous | -0.447 | Destabilizing | 0.364 | N | 0.387 | neutral | None | None | None | None | N |
| M/T | 0.1926 | likely_benign | 0.2425 | benign | -0.352 | Destabilizing | 0.175 | N | 0.38 | neutral | N | 0.428088121 | None | None | N |
| M/V | 0.1021 | likely_benign | 0.1193 | benign | -0.45 | Destabilizing | 0.019 | N | 0.231 | neutral | N | 0.44960014 | None | None | N |
| M/W | 0.7398 | likely_pathogenic | 0.8151 | pathogenic | -0.167 | Destabilizing | 0.958 | D | 0.377 | neutral | None | None | None | None | N |
| M/Y | 0.6434 | likely_pathogenic | 0.7247 | pathogenic | -0.09 | Destabilizing | 0.667 | D | 0.428 | 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.