Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29090 | 87493;87494;87495 | chr2:178558086;178558085;178558084 | chr2:179422813;179422812;179422811 |
| N2AB | 27449 | 82570;82571;82572 | chr2:178558086;178558085;178558084 | chr2:179422813;179422812;179422811 |
| N2A | 26522 | 79789;79790;79791 | chr2:178558086;178558085;178558084 | chr2:179422813;179422812;179422811 |
| N2B | 20025 | 60298;60299;60300 | chr2:178558086;178558085;178558084 | chr2:179422813;179422812;179422811 |
| Novex-1 | 20150 | 60673;60674;60675 | chr2:178558086;178558085;178558084 | chr2:179422813;179422812;179422811 |
| Novex-2 | 20217 | 60874;60875;60876 | chr2:178558086;178558085;178558084 | chr2:179422813;179422812;179422811 |
| 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 | 0.997 | N | 0.473 | 0.283 | 0.379881503574 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 6.33473E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/S | rs1335648809  |
None | 1.0 | N | 0.737 | 0.428 | 0.308278614506 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 7.24E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/S | rs1335648809 |
None | 1.0 | N | 0.737 | 0.428 | 0.308278614506 | gnomAD-4.0.0 | 1.36833E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79886E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.9306 | likely_pathogenic | 0.9511 | pathogenic | -0.857 | Destabilizing | 0.999 | D | 0.565 | neutral | None | None | None | None | N |
| R/C | 0.5966 | likely_pathogenic | 0.6712 | pathogenic | -0.792 | Destabilizing | 1.0 | D | 0.71 | prob.delet. | None | None | None | None | N |
| R/D | 0.9557 | likely_pathogenic | 0.9663 | pathogenic | 0.021 | Stabilizing | 1.0 | D | 0.719 | prob.delet. | None | None | None | None | N |
| R/E | 0.8969 | likely_pathogenic | 0.9223 | pathogenic | 0.168 | Stabilizing | 0.999 | D | 0.592 | neutral | None | None | None | None | N |
| R/F | 0.9541 | likely_pathogenic | 0.9663 | pathogenic | -0.575 | Destabilizing | 1.0 | D | 0.705 | prob.neutral | None | None | None | None | N |
| R/G | 0.8521 | likely_pathogenic | 0.8888 | pathogenic | -1.192 | Destabilizing | 1.0 | D | 0.69 | prob.neutral | N | 0.483678779 | None | None | N |
| R/H | 0.368 | ambiguous | 0.4098 | ambiguous | -1.443 | Destabilizing | 1.0 | D | 0.687 | prob.neutral | None | None | None | None | N |
| R/I | 0.8517 | likely_pathogenic | 0.8928 | pathogenic | 0.054 | Stabilizing | 1.0 | D | 0.721 | prob.delet. | N | 0.484692737 | None | None | N |
| R/K | 0.5 | ambiguous | 0.521 | ambiguous | -0.784 | Destabilizing | 0.997 | D | 0.473 | neutral | N | 0.46278614 | None | None | N |
| R/L | 0.7852 | likely_pathogenic | 0.836 | pathogenic | 0.054 | Stabilizing | 1.0 | D | 0.69 | prob.neutral | None | None | None | None | N |
| R/M | 0.9036 | likely_pathogenic | 0.9303 | pathogenic | -0.343 | Destabilizing | 1.0 | D | 0.695 | prob.neutral | None | None | None | None | N |
| R/N | 0.9155 | likely_pathogenic | 0.9309 | pathogenic | -0.322 | Destabilizing | 1.0 | D | 0.707 | prob.neutral | None | None | None | None | N |
| R/P | 0.9487 | likely_pathogenic | 0.957 | pathogenic | -0.229 | Destabilizing | 1.0 | D | 0.691 | prob.neutral | None | None | None | None | N |
| R/Q | 0.4474 | ambiguous | 0.4935 | ambiguous | -0.427 | Destabilizing | 1.0 | D | 0.697 | prob.neutral | None | None | None | None | N |
| R/S | 0.9426 | likely_pathogenic | 0.9585 | pathogenic | -1.13 | Destabilizing | 1.0 | D | 0.737 | prob.delet. | N | 0.472575964 | None | None | N |
| R/T | 0.8897 | likely_pathogenic | 0.9175 | pathogenic | -0.786 | Destabilizing | 1.0 | D | 0.734 | prob.delet. | N | 0.495288574 | None | None | N |
| R/V | 0.9089 | likely_pathogenic | 0.9335 | pathogenic | -0.229 | Destabilizing | 1.0 | D | 0.717 | prob.delet. | None | None | None | None | N |
| R/W | 0.6151 | likely_pathogenic | 0.6578 | pathogenic | -0.2 | Destabilizing | 1.0 | D | 0.715 | prob.delet. | None | None | None | None | N |
| R/Y | 0.8113 | likely_pathogenic | 0.844 | pathogenic | 0.072 | Stabilizing | 1.0 | D | 0.709 | prob.delet. | 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.