Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21216 | 63871;63872;63873 | chr2:178587663;178587662;178587661 | chr2:179452390;179452389;179452388 |
| N2AB | 19575 | 58948;58949;58950 | chr2:178587663;178587662;178587661 | chr2:179452390;179452389;179452388 |
| N2A | 18648 | 56167;56168;56169 | chr2:178587663;178587662;178587661 | chr2:179452390;179452389;179452388 |
| N2B | 12151 | 36676;36677;36678 | chr2:178587663;178587662;178587661 | chr2:179452390;179452389;179452388 |
| Novex-1 | 12276 | 37051;37052;37053 | chr2:178587663;178587662;178587661 | chr2:179452390;179452389;179452388 |
| Novex-2 | 12343 | 37252;37253;37254 | chr2:178587663;178587662;178587661 | chr2:179452390;179452389;179452388 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/M | rs542681131  |
-0.362 | 1.0 | N | 0.619 | 0.293 | 0.512595481341 | gnomAD-2.1.1 | 2.82E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 2.28938E-04 | None | 0 | 0 | 0 |
| V/M | rs542681131 |
-0.362 | 1.0 | N | 0.619 | 0.293 | 0.512595481341 | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 8.28157E-04 | 0 |
| V/M | rs542681131 |
-0.362 | 1.0 | N | 0.619 | 0.293 | 0.512595481341 | 1000 genomes | 1.99681E-04 | None | None | None | None | I | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 1E-03 | None |
| V/M | rs542681131 |
-0.362 | 1.0 | N | 0.619 | 0.293 | 0.512595481341 | gnomAD-4.0.0 | 1.98398E-05 | None | None | None | None | I | None | 1.33397E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 3.29504E-04 | 1.60159E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.3783 | ambiguous | 0.3732 | ambiguous | -1.583 | Destabilizing | 0.999 | D | 0.535 | neutral | N | 0.484069866 | None | None | I |
| V/C | 0.8571 | likely_pathogenic | 0.88 | pathogenic | -1.195 | Destabilizing | 1.0 | D | 0.617 | neutral | None | None | None | None | I |
| V/D | 0.7506 | likely_pathogenic | 0.7394 | pathogenic | -1.161 | Destabilizing | 1.0 | D | 0.695 | prob.neutral | None | None | None | None | I |
| V/E | 0.7017 | likely_pathogenic | 0.692 | pathogenic | -1.036 | Destabilizing | 1.0 | D | 0.667 | neutral | N | 0.445359549 | None | None | I |
| V/F | 0.4533 | ambiguous | 0.4597 | ambiguous | -0.894 | Destabilizing | 1.0 | D | 0.652 | neutral | None | None | None | None | I |
| V/G | 0.521 | ambiguous | 0.5133 | ambiguous | -2.03 | Highly Destabilizing | 1.0 | D | 0.699 | prob.neutral | N | 0.501559548 | None | None | I |
| V/H | 0.879 | likely_pathogenic | 0.8899 | pathogenic | -1.537 | Destabilizing | 1.0 | D | 0.67 | neutral | None | None | None | None | I |
| V/I | 0.1027 | likely_benign | 0.103 | benign | -0.404 | Destabilizing | 0.998 | D | 0.465 | neutral | None | None | None | None | I |
| V/K | 0.7933 | likely_pathogenic | 0.7948 | pathogenic | -1.315 | Destabilizing | 1.0 | D | 0.667 | neutral | None | None | None | None | I |
| V/L | 0.4294 | ambiguous | 0.4369 | ambiguous | -0.404 | Destabilizing | 0.997 | D | 0.542 | neutral | N | 0.38449473 | None | None | I |
| V/M | 0.3359 | likely_benign | 0.3402 | ambiguous | -0.465 | Destabilizing | 1.0 | D | 0.619 | neutral | N | 0.504887855 | None | None | I |
| V/N | 0.6804 | likely_pathogenic | 0.6839 | pathogenic | -1.324 | Destabilizing | 1.0 | D | 0.692 | prob.neutral | None | None | None | None | I |
| V/P | 0.7214 | likely_pathogenic | 0.7082 | pathogenic | -0.763 | Destabilizing | 1.0 | D | 0.673 | neutral | None | None | None | None | I |
| V/Q | 0.7474 | likely_pathogenic | 0.7516 | pathogenic | -1.264 | Destabilizing | 1.0 | D | 0.669 | neutral | None | None | None | None | I |
| V/R | 0.7547 | likely_pathogenic | 0.7491 | pathogenic | -1.067 | Destabilizing | 1.0 | D | 0.69 | prob.neutral | None | None | None | None | I |
| V/S | 0.577 | likely_pathogenic | 0.5802 | pathogenic | -2.003 | Highly Destabilizing | 1.0 | D | 0.686 | prob.neutral | None | None | None | None | I |
| V/T | 0.3686 | ambiguous | 0.3787 | ambiguous | -1.73 | Destabilizing | 0.999 | D | 0.595 | neutral | None | None | None | None | I |
| V/W | 0.9515 | likely_pathogenic | 0.9559 | pathogenic | -1.18 | Destabilizing | 1.0 | D | 0.688 | prob.neutral | None | None | None | None | I |
| V/Y | 0.8359 | likely_pathogenic | 0.844 | pathogenic | -0.838 | Destabilizing | 1.0 | D | 0.657 | 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.