Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 35172 | 105739;105740;105741 | chr2:178531101;178531100;178531099 | chr2:179395828;179395827;179395826 |
| N2AB | 33531 | 100816;100817;100818 | chr2:178531101;178531100;178531099 | chr2:179395828;179395827;179395826 |
| N2A | 32604 | 98035;98036;98037 | chr2:178531101;178531100;178531099 | chr2:179395828;179395827;179395826 |
| N2B | 26107 | 78544;78545;78546 | chr2:178531101;178531100;178531099 | chr2:179395828;179395827;179395826 |
| Novex-1 | 26232 | 78919;78920;78921 | chr2:178531101;178531100;178531099 | chr2:179395828;179395827;179395826 |
| Novex-2 | 26299 | 79120;79121;79122 | chr2:178531101;178531100;178531099 | chr2:179395828;179395827;179395826 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/F | rs749354699  |
-0.905 | 0.999 | N | 0.605 | 0.476 | 0.582419091513 | gnomAD-2.1.1 | 1.78E-05 | None | None | None | None | N | None | 0 | 1.41347E-04 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| S/F | rs749354699 |
-0.905 | 0.999 | N | 0.605 | 0.476 | 0.582419091513 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 0 | 1.96386E-04 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/F | rs749354699 |
-0.905 | 0.999 | N | 0.605 | 0.476 | 0.582419091513 | gnomAD-4.0.0 | 8.97273E-06 | None | None | None | None | N | None | 0 | 1.1862E-04 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/Y | rs749354699 |
-0.656 | 0.999 | N | 0.605 | 0.489 | 0.582419091513 | gnomAD-2.1.1 | 4.01E-06 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| S/Y | rs749354699 |
-0.656 | 0.999 | N | 0.605 | 0.489 | 0.582419091513 | gnomAD-4.0.0 | 1.59224E-06 | None | None | None | None | N | None | 0 | 2.28645E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.105 | likely_benign | 0.1101 | benign | -0.226 | Destabilizing | 0.934 | D | 0.352 | neutral | N | 0.50933367 | None | None | N |
| S/C | 0.2445 | likely_benign | 0.237 | benign | -0.167 | Destabilizing | 1.0 | D | 0.533 | neutral | N | 0.506947595 | None | None | N |
| S/D | 0.4599 | ambiguous | 0.4548 | ambiguous | 0.016 | Stabilizing | 0.989 | D | 0.428 | neutral | None | None | None | None | N |
| S/E | 0.6596 | likely_pathogenic | 0.6512 | pathogenic | -0.094 | Destabilizing | 0.996 | D | 0.428 | neutral | None | None | None | None | N |
| S/F | 0.3331 | likely_benign | 0.3329 | benign | -0.931 | Destabilizing | 0.999 | D | 0.605 | neutral | N | 0.48858985 | None | None | N |
| S/G | 0.1283 | likely_benign | 0.1256 | benign | -0.297 | Destabilizing | 0.057 | N | 0.235 | neutral | None | None | None | None | N |
| S/H | 0.5497 | ambiguous | 0.5242 | ambiguous | -0.78 | Destabilizing | 1.0 | D | 0.509 | neutral | None | None | None | None | N |
| S/I | 0.3827 | ambiguous | 0.3865 | ambiguous | -0.172 | Destabilizing | 0.999 | D | 0.602 | neutral | None | None | None | None | N |
| S/K | 0.854 | likely_pathogenic | 0.8443 | pathogenic | -0.398 | Destabilizing | 0.989 | D | 0.455 | neutral | None | None | None | None | N |
| S/L | 0.1686 | likely_benign | 0.1764 | benign | -0.172 | Destabilizing | 0.999 | D | 0.557 | neutral | None | None | None | None | N |
| S/M | 0.3478 | ambiguous | 0.3492 | ambiguous | 0.049 | Stabilizing | 1.0 | D | 0.52 | neutral | None | None | None | None | N |
| S/N | 0.255 | likely_benign | 0.2471 | benign | -0.073 | Destabilizing | 0.989 | D | 0.45 | neutral | None | None | None | None | N |
| S/P | 0.5157 | ambiguous | 0.5667 | pathogenic | -0.164 | Destabilizing | 0.999 | D | 0.516 | neutral | N | 0.466433444 | None | None | N |
| S/Q | 0.7294 | likely_pathogenic | 0.7085 | pathogenic | -0.336 | Destabilizing | 0.999 | D | 0.473 | neutral | None | None | None | None | N |
| S/R | 0.7836 | likely_pathogenic | 0.7692 | pathogenic | -0.169 | Destabilizing | 0.999 | D | 0.506 | neutral | None | None | None | None | N |
| S/T | 0.103 | likely_benign | 0.1048 | benign | -0.172 | Destabilizing | 0.986 | D | 0.401 | neutral | N | 0.503426418 | None | None | N |
| S/V | 0.3201 | likely_benign | 0.3215 | benign | -0.164 | Destabilizing | 0.999 | D | 0.609 | neutral | None | None | None | None | N |
| S/W | 0.5257 | ambiguous | 0.5011 | ambiguous | -0.99 | Destabilizing | 1.0 | D | 0.698 | prob.neutral | None | None | None | None | N |
| S/Y | 0.3436 | ambiguous | 0.3414 | ambiguous | -0.687 | Destabilizing | 0.999 | D | 0.605 | neutral | N | 0.48858985 | 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.