Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31380 | 94363;94364;94365 | chr2:178547488;178547487;178547486 | chr2:179412215;179412214;179412213 |
| N2AB | 29739 | 89440;89441;89442 | chr2:178547488;178547487;178547486 | chr2:179412215;179412214;179412213 |
| N2A | 28812 | 86659;86660;86661 | chr2:178547488;178547487;178547486 | chr2:179412215;179412214;179412213 |
| N2B | 22315 | 67168;67169;67170 | chr2:178547488;178547487;178547486 | chr2:179412215;179412214;179412213 |
| Novex-1 | 22440 | 67543;67544;67545 | chr2:178547488;178547487;178547486 | chr2:179412215;179412214;179412213 |
| Novex-2 | 22507 | 67744;67745;67746 | chr2:178547488;178547487;178547486 | chr2:179412215;179412214;179412213 |
| 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/A | rs764500703  |
-0.344 | 0.005 | N | 0.458 | 0.097 | 0.273070737957 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 0 | 8.74E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| S/A | rs764500703 |
-0.344 | 0.005 | N | 0.458 | 0.097 | 0.273070737957 | gnomAD-4.0.0 | 4.7789E-06 | None | None | None | None | N | None | 0 | 6.87128E-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 | 0.0763 | likely_benign | 0.0842 | benign | -1.066 | Destabilizing | 0.005 | N | 0.458 | neutral | N | 0.428611733 | None | None | N |
| S/C | 0.061 | likely_benign | 0.058 | benign | -0.492 | Destabilizing | None | N | 0.569 | neutral | N | 0.466823404 | None | None | N |
| S/D | 0.5973 | likely_pathogenic | 0.6189 | pathogenic | -1.549 | Destabilizing | 0.072 | N | 0.651 | neutral | None | None | None | None | N |
| S/E | 0.6002 | likely_pathogenic | 0.6383 | pathogenic | -1.29 | Destabilizing | 0.072 | N | 0.651 | neutral | None | None | None | None | N |
| S/F | 0.1696 | likely_benign | 0.1991 | benign | -0.722 | Destabilizing | 0.295 | N | 0.701 | prob.neutral | N | 0.439540802 | None | None | N |
| S/G | 0.1363 | likely_benign | 0.1238 | benign | -1.482 | Destabilizing | 0.031 | N | 0.599 | neutral | None | None | None | None | N |
| S/H | 0.2652 | likely_benign | 0.2607 | benign | -1.534 | Destabilizing | 0.628 | D | 0.684 | prob.neutral | None | None | None | None | N |
| S/I | 0.1037 | likely_benign | 0.1164 | benign | 0.031 | Stabilizing | 0.038 | N | 0.715 | prob.delet. | None | None | None | None | N |
| S/K | 0.6509 | likely_pathogenic | 0.6763 | pathogenic | 0.047 | Stabilizing | 0.072 | N | 0.642 | neutral | None | None | None | None | N |
| S/L | 0.0908 | likely_benign | 0.0974 | benign | 0.031 | Stabilizing | 0.016 | N | 0.697 | prob.neutral | None | None | None | None | N |
| S/M | 0.1298 | likely_benign | 0.1588 | benign | -0.275 | Destabilizing | 0.356 | N | 0.694 | prob.neutral | None | None | None | None | N |
| S/N | 0.1608 | likely_benign | 0.1684 | benign | -0.768 | Destabilizing | 0.072 | N | 0.643 | neutral | None | None | None | None | N |
| S/P | 0.9556 | likely_pathogenic | 0.9512 | pathogenic | -0.304 | Destabilizing | 0.106 | N | 0.735 | prob.delet. | N | 0.519175022 | None | None | N |
| S/Q | 0.4066 | ambiguous | 0.425 | ambiguous | -0.399 | Destabilizing | 0.356 | N | 0.691 | prob.neutral | None | None | None | None | N |
| S/R | 0.5225 | ambiguous | 0.5339 | ambiguous | -0.481 | Destabilizing | 0.072 | N | 0.748 | deleterious | None | None | None | None | N |
| S/T | 0.0526 | likely_benign | 0.0595 | benign | -0.407 | Destabilizing | None | N | 0.253 | neutral | N | 0.396555243 | None | None | N |
| S/V | 0.1055 | likely_benign | 0.1162 | benign | -0.304 | Destabilizing | 0.016 | N | 0.701 | prob.neutral | None | None | None | None | N |
| S/W | 0.324 | likely_benign | 0.3294 | benign | -1.005 | Destabilizing | 0.864 | D | 0.726 | prob.delet. | None | None | None | None | N |
| S/Y | 0.1627 | likely_benign | 0.1665 | benign | -0.544 | Destabilizing | 0.295 | N | 0.691 | prob.neutral | N | 0.433172191 | 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.