Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31308 | 94147;94148;94149 | chr2:178547704;178547703;178547702 | chr2:179412431;179412430;179412429 |
| N2AB | 29667 | 89224;89225;89226 | chr2:178547704;178547703;178547702 | chr2:179412431;179412430;179412429 |
| N2A | 28740 | 86443;86444;86445 | chr2:178547704;178547703;178547702 | chr2:179412431;179412430;179412429 |
| N2B | 22243 | 66952;66953;66954 | chr2:178547704;178547703;178547702 | chr2:179412431;179412430;179412429 |
| Novex-1 | 22368 | 67327;67328;67329 | chr2:178547704;178547703;178547702 | chr2:179412431;179412430;179412429 |
| Novex-2 | 22435 | 67528;67529;67530 | chr2:178547704;178547703;178547702 | chr2:179412431;179412430;179412429 |
| 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 | None | None | 0.355 | N | 0.279 | 0.164 | 0.184867976434 | gnomAD-4.0.0 | 1.36834E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79886E-06 | 0 | 0 |
| R/M | None | None | 1.0 | N | 0.577 | 0.325 | 0.305086939656 | gnomAD-4.0.0 | 6.8417E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99431E-07 | 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 | 0.7073 | likely_pathogenic | 0.6579 | pathogenic | -0.198 | Destabilizing | 0.982 | D | 0.575 | neutral | None | None | None | None | I |
| R/C | 0.2871 | likely_benign | 0.2796 | benign | -0.352 | Destabilizing | 1.0 | D | 0.853 | deleterious | None | None | None | None | I |
| R/D | 0.9221 | likely_pathogenic | 0.9101 | pathogenic | -0.06 | Destabilizing | 0.997 | D | 0.773 | deleterious | None | None | None | None | I |
| R/E | 0.6915 | likely_pathogenic | 0.659 | pathogenic | 0.016 | Stabilizing | 0.982 | D | 0.524 | neutral | None | None | None | None | I |
| R/F | 0.7843 | likely_pathogenic | 0.7654 | pathogenic | -0.362 | Destabilizing | 0.999 | D | 0.814 | deleterious | None | None | None | None | I |
| R/G | 0.6615 | likely_pathogenic | 0.6235 | pathogenic | -0.414 | Destabilizing | 0.988 | D | 0.523 | neutral | N | 0.475784605 | None | None | I |
| R/H | 0.2006 | likely_benign | 0.2083 | benign | -0.831 | Destabilizing | 0.999 | D | 0.594 | neutral | None | None | None | None | I |
| R/I | 0.4203 | ambiguous | 0.3829 | ambiguous | 0.341 | Stabilizing | 0.999 | D | 0.844 | deleterious | None | None | None | None | I |
| R/K | 0.1419 | likely_benign | 0.1357 | benign | -0.278 | Destabilizing | 0.355 | N | 0.279 | neutral | N | 0.39798689 | None | None | I |
| R/L | 0.4287 | ambiguous | 0.4161 | ambiguous | 0.341 | Stabilizing | 0.991 | D | 0.523 | neutral | None | None | None | None | I |
| R/M | 0.5072 | ambiguous | 0.4853 | ambiguous | -0.067 | Destabilizing | 1.0 | D | 0.577 | neutral | N | 0.464681789 | None | None | I |
| R/N | 0.8236 | likely_pathogenic | 0.8017 | pathogenic | -0.015 | Destabilizing | 0.997 | D | 0.601 | neutral | None | None | None | None | I |
| R/P | 0.5254 | ambiguous | 0.4831 | ambiguous | 0.182 | Stabilizing | 0.999 | D | 0.851 | deleterious | None | None | None | None | I |
| R/Q | 0.1751 | likely_benign | 0.1785 | benign | -0.134 | Destabilizing | 0.995 | D | 0.64 | neutral | None | None | None | None | I |
| R/S | 0.7883 | likely_pathogenic | 0.7665 | pathogenic | -0.468 | Destabilizing | 0.976 | D | 0.663 | prob.neutral | N | 0.452400431 | None | None | I |
| R/T | 0.5897 | likely_pathogenic | 0.5491 | ambiguous | -0.248 | Destabilizing | 0.997 | D | 0.559 | neutral | N | 0.486550024 | None | None | I |
| R/V | 0.5535 | ambiguous | 0.5092 | ambiguous | 0.182 | Stabilizing | 0.997 | D | 0.833 | deleterious | None | None | None | None | I |
| R/W | 0.3697 | ambiguous | 0.3994 | ambiguous | -0.329 | Destabilizing | 1.0 | D | 0.874 | deleterious | N | 0.476291584 | None | None | I |
| R/Y | 0.6089 | likely_pathogenic | 0.6174 | pathogenic | 0.057 | Stabilizing | 0.999 | D | 0.833 | deleterious | None | None | 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.