Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 3091 | 9496;9497;9498 | chr2:178768048;178768047;178768046 | chr2:179632775;179632774;179632773 |
| N2AB | 3091 | 9496;9497;9498 | chr2:178768048;178768047;178768046 | chr2:179632775;179632774;179632773 |
| N2A | 3091 | 9496;9497;9498 | chr2:178768048;178768047;178768046 | chr2:179632775;179632774;179632773 |
| N2B | 3045 | 9358;9359;9360 | chr2:178768048;178768047;178768046 | chr2:179632775;179632774;179632773 |
| Novex-1 | 3045 | 9358;9359;9360 | chr2:178768048;178768047;178768046 | chr2:179632775;179632774;179632773 |
| Novex-2 | 3045 | 9358;9359;9360 | chr2:178768048;178768047;178768046 | chr2:179632775;179632774;179632773 |
| Novex-3 | 3091 | 9496;9497;9498 | chr2:178768048;178768047;178768046 | chr2:179632775;179632774;179632773 |
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 | 0.828 | N | 0.563 | 0.318 | 0.316198179892 | gnomAD-4.0.0 | 2.05222E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.69788E-06 | 0 | 0 |
| M/R | None | None | 0.998 | N | 0.561 | 0.459 | 0.459009637647 | gnomAD-4.0.0 | 7.20193E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 7.87501E-06 | 0 | 0 |
| M/V | rs1307544270  |
None | 0.828 | N | 0.495 | 0.274 | 0.29527378943 | gnomAD-4.0.0 | 6.84074E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99292E-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 | 0.8925 | likely_pathogenic | 0.8636 | pathogenic | -2.348 | Highly Destabilizing | 0.963 | D | 0.509 | neutral | None | None | None | None | N |
| M/C | 0.9012 | likely_pathogenic | 0.877 | pathogenic | -2.21 | Highly Destabilizing | 1.0 | D | 0.538 | neutral | None | None | None | None | N |
| M/D | 0.9898 | likely_pathogenic | 0.9868 | pathogenic | -1.905 | Destabilizing | 0.999 | D | 0.621 | neutral | None | None | None | None | N |
| M/E | 0.8554 | likely_pathogenic | 0.8248 | pathogenic | -1.77 | Destabilizing | 0.999 | D | 0.587 | neutral | None | None | None | None | N |
| M/F | 0.4292 | ambiguous | 0.3435 | ambiguous | -0.993 | Destabilizing | 0.969 | D | 0.543 | neutral | None | None | None | None | N |
| M/G | 0.9313 | likely_pathogenic | 0.9148 | pathogenic | -2.757 | Highly Destabilizing | 0.999 | D | 0.611 | neutral | None | None | None | None | N |
| M/H | 0.7749 | likely_pathogenic | 0.7126 | pathogenic | -2.106 | Highly Destabilizing | 1.0 | D | 0.587 | neutral | None | None | None | None | N |
| M/I | 0.6883 | likely_pathogenic | 0.6198 | pathogenic | -1.211 | Destabilizing | 0.828 | D | 0.563 | neutral | N | 0.32168291 | None | None | N |
| M/K | 0.3795 | ambiguous | 0.313 | benign | -1.415 | Destabilizing | 0.993 | D | 0.509 | neutral | N | 0.342223885 | None | None | N |
| M/L | 0.2245 | likely_benign | 0.1906 | benign | -1.211 | Destabilizing | 0.03 | N | 0.247 | neutral | N | 0.333911552 | None | None | N |
| M/N | 0.8826 | likely_pathogenic | 0.8611 | pathogenic | -1.512 | Destabilizing | 0.999 | D | 0.592 | neutral | None | None | None | None | N |
| M/P | 0.999 | likely_pathogenic | 0.9986 | pathogenic | -1.569 | Destabilizing | 0.999 | D | 0.594 | neutral | None | None | None | None | N |
| M/Q | 0.4482 | ambiguous | 0.4036 | ambiguous | -1.423 | Destabilizing | 0.999 | D | 0.551 | neutral | None | None | None | None | N |
| M/R | 0.4106 | ambiguous | 0.3357 | benign | -1.181 | Destabilizing | 0.998 | D | 0.561 | neutral | N | 0.343317545 | None | None | N |
| M/S | 0.8672 | likely_pathogenic | 0.8329 | pathogenic | -2.124 | Highly Destabilizing | 0.995 | D | 0.509 | neutral | None | None | None | None | N |
| M/T | 0.7148 | likely_pathogenic | 0.6529 | pathogenic | -1.874 | Destabilizing | 0.979 | D | 0.497 | neutral | N | 0.340206575 | None | None | N |
| M/V | 0.2819 | likely_benign | 0.2502 | benign | -1.569 | Destabilizing | 0.828 | D | 0.495 | neutral | N | 0.323388541 | None | None | N |
| M/W | 0.7561 | likely_pathogenic | 0.6613 | pathogenic | -1.151 | Destabilizing | 1.0 | D | 0.547 | neutral | None | None | None | None | N |
| M/Y | 0.7148 | likely_pathogenic | 0.6289 | pathogenic | -1.177 | Destabilizing | 0.999 | D | 0.567 | 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.