Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1483 | 4672;4673;4674 | chr2:178777737;178777736;178777735 | chr2:179642464;179642463;179642462 |
| N2AB | 1483 | 4672;4673;4674 | chr2:178777737;178777736;178777735 | chr2:179642464;179642463;179642462 |
| N2A | 1483 | 4672;4673;4674 | chr2:178777737;178777736;178777735 | chr2:179642464;179642463;179642462 |
| N2B | 1437 | 4534;4535;4536 | chr2:178777737;178777736;178777735 | chr2:179642464;179642463;179642462 |
| Novex-1 | 1437 | 4534;4535;4536 | chr2:178777737;178777736;178777735 | chr2:179642464;179642463;179642462 |
| Novex-2 | 1437 | 4534;4535;4536 | chr2:178777737;178777736;178777735 | chr2:179642464;179642463;179642462 |
| Novex-3 | 1483 | 4672;4673;4674 | chr2:178777737;178777736;178777735 | chr2:179642464;179642463;179642462 |
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/S | rs546160098  |
0.012 | 0.942 | N | 0.591 | 0.425 | 0.475112344478 | gnomAD-2.1.1 | 2.13E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 1.99124E-04 | 7.77E-06 | 0 |
| R/S | rs546160098 |
0.012 | 0.942 | N | 0.591 | 0.425 | 0.475112344478 | gnomAD-3.1.2 | 3.28E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 3.76648E-04 | 0 | 1.47E-05 | 0 | 0 |
| R/S | rs546160098 |
0.012 | 0.942 | N | 0.591 | 0.425 | 0.475112344478 | 1000 genomes | 1.99681E-04 | None | None | None | None | I | None | 0 | 0 | None | None | 0 | 1E-03 | None | None | None | 0 | None |
| R/S | rs546160098 |
0.012 | 0.942 | N | 0.591 | 0.425 | 0.475112344478 | gnomAD-4.0.0 | 1.92068E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 2.03909E-04 | 0 | 4.78391E-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 | 0.9633 | likely_pathogenic | 0.9559 | pathogenic | 0.019 | Stabilizing | 0.754 | D | 0.607 | neutral | None | None | None | None | I |
| R/C | 0.86 | likely_pathogenic | 0.8297 | pathogenic | -0.25 | Destabilizing | 0.994 | D | 0.649 | neutral | None | None | None | None | I |
| R/D | 0.9839 | likely_pathogenic | 0.9802 | pathogenic | -0.36 | Destabilizing | 0.993 | D | 0.619 | neutral | None | None | None | None | I |
| R/E | 0.9306 | likely_pathogenic | 0.9188 | pathogenic | -0.326 | Destabilizing | 0.926 | D | 0.619 | neutral | None | None | None | None | I |
| R/F | 0.9517 | likely_pathogenic | 0.9421 | pathogenic | -0.308 | Destabilizing | 0.956 | D | 0.63 | neutral | None | None | None | None | I |
| R/G | 0.9529 | likely_pathogenic | 0.9335 | pathogenic | -0.108 | Destabilizing | 0.904 | D | 0.587 | neutral | D | 0.645448939 | None | None | I |
| R/H | 0.5888 | likely_pathogenic | 0.5611 | ambiguous | -0.598 | Destabilizing | 0.998 | D | 0.595 | neutral | None | None | None | None | I |
| R/I | 0.8827 | likely_pathogenic | 0.8691 | pathogenic | 0.307 | Stabilizing | 0.444 | N | 0.599 | neutral | N | 0.509549353 | None | None | I |
| R/K | 0.6142 | likely_pathogenic | 0.5647 | pathogenic | -0.196 | Destabilizing | 0.795 | D | 0.527 | neutral | N | 0.500231471 | None | None | I |
| R/L | 0.8282 | likely_pathogenic | 0.8084 | pathogenic | 0.307 | Stabilizing | 0.754 | D | 0.604 | neutral | None | None | None | None | I |
| R/M | 0.9235 | likely_pathogenic | 0.9099 | pathogenic | -0.105 | Destabilizing | 0.956 | D | 0.603 | neutral | None | None | None | None | I |
| R/N | 0.9621 | likely_pathogenic | 0.9575 | pathogenic | -0.096 | Destabilizing | 0.993 | D | 0.597 | neutral | None | None | None | None | I |
| R/P | 0.9823 | likely_pathogenic | 0.9782 | pathogenic | 0.228 | Stabilizing | 0.993 | D | 0.618 | neutral | None | None | None | None | I |
| R/Q | 0.6036 | likely_pathogenic | 0.5656 | pathogenic | -0.134 | Destabilizing | 0.993 | D | 0.606 | neutral | None | None | None | None | I |
| R/S | 0.9477 | likely_pathogenic | 0.9379 | pathogenic | -0.25 | Destabilizing | 0.942 | D | 0.591 | neutral | N | 0.494374704 | None | None | I |
| R/T | 0.9326 | likely_pathogenic | 0.9258 | pathogenic | -0.118 | Destabilizing | 0.822 | D | 0.622 | neutral | N | 0.499350268 | None | None | I |
| R/V | 0.9198 | likely_pathogenic | 0.9108 | pathogenic | 0.228 | Stabilizing | 0.019 | N | 0.583 | neutral | None | None | None | None | I |
| R/W | 0.7709 | likely_pathogenic | 0.7373 | pathogenic | -0.505 | Destabilizing | 0.998 | D | 0.681 | prob.neutral | None | None | None | None | I |
| R/Y | 0.8968 | likely_pathogenic | 0.8822 | pathogenic | -0.109 | Destabilizing | 0.978 | D | 0.625 | neutral | 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.