Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2403 | 7432;7433;7434 | chr2:178773961;178773960;178773959 | chr2:179638688;179638687;179638686 |
| N2AB | 2403 | 7432;7433;7434 | chr2:178773961;178773960;178773959 | chr2:179638688;179638687;179638686 |
| N2A | 2403 | 7432;7433;7434 | chr2:178773961;178773960;178773959 | chr2:179638688;179638687;179638686 |
| N2B | 2357 | 7294;7295;7296 | chr2:178773961;178773960;178773959 | chr2:179638688;179638687;179638686 |
| Novex-1 | 2357 | 7294;7295;7296 | chr2:178773961;178773960;178773959 | chr2:179638688;179638687;179638686 |
| Novex-2 | 2357 | 7294;7295;7296 | chr2:178773961;178773960;178773959 | chr2:179638688;179638687;179638686 |
| Novex-3 | 2403 | 7432;7433;7434 | chr2:178773961;178773960;178773959 | chr2:179638688;179638687;179638686 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/T | rs760895168  |
-2.55 | 0.338 | D | 0.559 | 0.418 | 0.739716253508 | gnomAD-2.1.1 | 3.98E-06 | None | None | None | None | N | None | 0 | 2.89E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/T | rs760895168 |
-2.55 | 0.338 | D | 0.559 | 0.418 | 0.739716253508 | gnomAD-4.0.0 | 9.57706E-06 | None | None | None | None | N | None | 0 | 2.23634E-05 | None | 0 | 0 | None | 0 | 0 | 1.07917E-05 | 0 | 1.65585E-05 |
| I/V | rs1415643045 |
-1.288 | 0.001 | N | 0.168 | 0.085 | 0.377451072189 | gnomAD-2.1.1 | 3.98E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.83E-06 | 0 |
| I/V | rs1415643045 |
-1.288 | 0.001 | N | 0.168 | 0.085 | 0.377451072189 | gnomAD-4.0.0 | 1.36815E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79861E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.3279 | likely_benign | 0.2973 | benign | -2.114 | Highly Destabilizing | 0.004 | N | 0.332 | neutral | None | None | None | None | N |
| I/C | 0.7086 | likely_pathogenic | 0.6793 | pathogenic | -1.209 | Destabilizing | 0.973 | D | 0.599 | neutral | None | None | None | None | N |
| I/D | 0.8764 | likely_pathogenic | 0.8486 | pathogenic | -2.213 | Highly Destabilizing | 0.826 | D | 0.713 | prob.delet. | None | None | None | None | N |
| I/E | 0.7273 | likely_pathogenic | 0.6807 | pathogenic | -2.064 | Highly Destabilizing | 0.826 | D | 0.703 | prob.neutral | None | None | None | None | N |
| I/F | 0.2056 | likely_benign | 0.1886 | benign | -1.296 | Destabilizing | 0.782 | D | 0.498 | neutral | N | 0.517027472 | None | None | N |
| I/G | 0.7656 | likely_pathogenic | 0.7289 | pathogenic | -2.566 | Highly Destabilizing | 0.704 | D | 0.659 | neutral | None | None | None | None | N |
| I/H | 0.6208 | likely_pathogenic | 0.5679 | pathogenic | -1.874 | Destabilizing | 0.991 | D | 0.719 | prob.delet. | None | None | None | None | N |
| I/K | 0.491 | ambiguous | 0.4342 | ambiguous | -1.691 | Destabilizing | 0.826 | D | 0.705 | prob.neutral | None | None | None | None | N |
| I/L | 0.1487 | likely_benign | 0.1391 | benign | -0.856 | Destabilizing | 0.084 | N | 0.38 | neutral | N | 0.511118087 | None | None | N |
| I/M | 0.0979 | likely_benign | 0.092 | benign | -0.624 | Destabilizing | 0.782 | D | 0.514 | neutral | N | 0.512155525 | None | None | N |
| I/N | 0.5061 | ambiguous | 0.4594 | ambiguous | -1.817 | Destabilizing | 0.879 | D | 0.725 | prob.delet. | D | 0.67520401 | None | None | N |
| I/P | 0.8658 | likely_pathogenic | 0.846 | pathogenic | -1.252 | Destabilizing | 0.906 | D | 0.721 | prob.delet. | None | None | None | None | N |
| I/Q | 0.5799 | likely_pathogenic | 0.5343 | ambiguous | -1.808 | Destabilizing | 0.906 | D | 0.723 | prob.delet. | None | None | None | None | N |
| I/R | 0.3928 | ambiguous | 0.3441 | ambiguous | -1.25 | Destabilizing | 0.826 | D | 0.721 | prob.delet. | None | None | None | None | N |
| I/S | 0.3936 | ambiguous | 0.3568 | ambiguous | -2.425 | Highly Destabilizing | 0.338 | N | 0.592 | neutral | D | 0.634466308 | None | None | N |
| I/T | 0.1697 | likely_benign | 0.1553 | benign | -2.147 | Highly Destabilizing | 0.338 | N | 0.559 | neutral | D | 0.551430834 | None | None | N |
| I/V | 0.0744 | likely_benign | 0.0708 | benign | -1.252 | Destabilizing | 0.001 | N | 0.168 | neutral | N | 0.503083732 | None | None | N |
| I/W | 0.8004 | likely_pathogenic | 0.7746 | pathogenic | -1.605 | Destabilizing | 0.991 | D | 0.728 | prob.delet. | None | None | None | None | N |
| I/Y | 0.5961 | likely_pathogenic | 0.5561 | ambiguous | -1.303 | Destabilizing | 0.906 | D | 0.601 | 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.