Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23541 | 70846;70847;70848 | chr2:178575511;178575510;178575509 | chr2:179440238;179440237;179440236 |
| N2AB | 21900 | 65923;65924;65925 | chr2:178575511;178575510;178575509 | chr2:179440238;179440237;179440236 |
| N2A | 20973 | 63142;63143;63144 | chr2:178575511;178575510;178575509 | chr2:179440238;179440237;179440236 |
| N2B | 14476 | 43651;43652;43653 | chr2:178575511;178575510;178575509 | chr2:179440238;179440237;179440236 |
| Novex-1 | 14601 | 44026;44027;44028 | chr2:178575511;178575510;178575509 | chr2:179440238;179440237;179440236 |
| Novex-2 | 14668 | 44227;44228;44229 | chr2:178575511;178575510;178575509 | chr2:179440238;179440237;179440236 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/N | None | None | 0.884 | N | 0.695 | 0.388 | 0.788637350915 | gnomAD-4.0.0 | 1.59146E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43295E-05 | 0 |
| I/T | None | None | 0.684 | N | 0.551 | 0.287 | 0.59007929581 | gnomAD-4.0.0 | 1.59146E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85894E-06 | 0 | 0 |
| I/V | None | None | 0.004 | N | 0.129 | 0.068 | 0.422040124859 | gnomAD-4.0.0 | 1.36848E-06 | None | None | None | None | N | None | 2.98829E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.15947E-05 | 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 | 0.8133 | likely_pathogenic | 0.8131 | pathogenic | -2.466 | Highly Destabilizing | 0.543 | D | 0.48 | neutral | None | None | None | None | N |
| I/C | 0.8437 | likely_pathogenic | 0.8616 | pathogenic | -1.682 | Destabilizing | 0.996 | D | 0.579 | neutral | None | None | None | None | N |
| I/D | 0.9681 | likely_pathogenic | 0.9697 | pathogenic | -2.164 | Highly Destabilizing | 0.91 | D | 0.697 | prob.neutral | None | None | None | None | N |
| I/E | 0.9535 | likely_pathogenic | 0.9518 | pathogenic | -2.004 | Highly Destabilizing | 0.742 | D | 0.691 | prob.neutral | None | None | None | None | N |
| I/F | 0.3949 | ambiguous | 0.3826 | ambiguous | -1.49 | Destabilizing | 0.939 | D | 0.539 | neutral | N | 0.470012432 | None | None | N |
| I/G | 0.9565 | likely_pathogenic | 0.9585 | pathogenic | -2.969 | Highly Destabilizing | 0.742 | D | 0.696 | prob.neutral | None | None | None | None | N |
| I/H | 0.9058 | likely_pathogenic | 0.9079 | pathogenic | -2.205 | Highly Destabilizing | 0.02 | N | 0.426 | neutral | None | None | None | None | N |
| I/K | 0.907 | likely_pathogenic | 0.9049 | pathogenic | -1.885 | Destabilizing | 0.91 | D | 0.7 | prob.neutral | None | None | None | None | N |
| I/L | 0.2215 | likely_benign | 0.2095 | benign | -1.054 | Destabilizing | 0.164 | N | 0.361 | neutral | N | 0.432516043 | None | None | N |
| I/M | 0.2481 | likely_benign | 0.2485 | benign | -0.882 | Destabilizing | 0.939 | D | 0.539 | neutral | N | 0.483854407 | None | None | N |
| I/N | 0.7975 | likely_pathogenic | 0.7945 | pathogenic | -1.97 | Destabilizing | 0.884 | D | 0.695 | prob.neutral | N | 0.495971181 | None | None | N |
| I/P | 0.867 | likely_pathogenic | 0.8718 | pathogenic | -1.5 | Destabilizing | 0.984 | D | 0.689 | prob.neutral | None | None | None | None | N |
| I/Q | 0.9216 | likely_pathogenic | 0.9167 | pathogenic | -1.938 | Destabilizing | 0.91 | D | 0.705 | prob.neutral | None | None | None | None | N |
| I/R | 0.868 | likely_pathogenic | 0.865 | pathogenic | -1.459 | Destabilizing | 0.91 | D | 0.695 | prob.neutral | None | None | None | None | N |
| I/S | 0.8216 | likely_pathogenic | 0.8282 | pathogenic | -2.728 | Highly Destabilizing | 0.684 | D | 0.636 | neutral | N | 0.475296032 | None | None | N |
| I/T | 0.7422 | likely_pathogenic | 0.741 | pathogenic | -2.423 | Highly Destabilizing | 0.684 | D | 0.551 | neutral | N | 0.475549521 | None | None | N |
| I/V | 0.0979 | likely_benign | 0.0972 | benign | -1.5 | Destabilizing | 0.004 | N | 0.129 | neutral | N | 0.398784684 | None | None | N |
| I/W | 0.925 | likely_pathogenic | 0.9354 | pathogenic | -1.723 | Destabilizing | 0.996 | D | 0.699 | prob.neutral | None | None | None | None | N |
| I/Y | 0.7963 | likely_pathogenic | 0.8019 | pathogenic | -1.489 | Destabilizing | 0.835 | D | 0.619 | 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.