Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24018 | 72277;72278;72279 | chr2:178574080;178574079;178574078 | chr2:179438807;179438806;179438805 |
| N2AB | 22377 | 67354;67355;67356 | chr2:178574080;178574079;178574078 | chr2:179438807;179438806;179438805 |
| N2A | 21450 | 64573;64574;64575 | chr2:178574080;178574079;178574078 | chr2:179438807;179438806;179438805 |
| N2B | 14953 | 45082;45083;45084 | chr2:178574080;178574079;178574078 | chr2:179438807;179438806;179438805 |
| Novex-1 | 15078 | 45457;45458;45459 | chr2:178574080;178574079;178574078 | chr2:179438807;179438806;179438805 |
| Novex-2 | 15145 | 45658;45659;45660 | chr2:178574080;178574079;178574078 | chr2:179438807;179438806;179438805 |
| 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/S | None | None | 0.997 | N | 0.764 | 0.517 | 0.715584271671 | gnomAD-4.0.0 | 1.59218E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86041E-06 | 0 | 0 |
| I/T | rs753170264  |
-2.219 | 0.976 | N | 0.696 | 0.358 | 0.493628743246 | gnomAD-2.1.1 | 8.05E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.78E-05 | 0 |
| I/T | rs753170264 |
-2.219 | 0.976 | N | 0.696 | 0.358 | 0.493628743246 | gnomAD-4.0.0 | 1.59218E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86041E-06 | 0 | 0 |
| I/V | None | None | 0.188 | N | 0.151 | 0.077 | 0.317667799068 | gnomAD-4.0.0 | 1.36874E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79934E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.8303 | likely_pathogenic | 0.8648 | pathogenic | -2.31 | Highly Destabilizing | 0.982 | D | 0.572 | neutral | None | None | None | None | N |
| I/C | 0.9235 | likely_pathogenic | 0.9292 | pathogenic | -1.495 | Destabilizing | 1.0 | D | 0.686 | prob.delet. | None | None | None | None | N |
| I/D | 0.9922 | likely_pathogenic | 0.9935 | pathogenic | -2.066 | Highly Destabilizing | 0.999 | D | 0.822 | deleterious | None | None | None | None | N |
| I/E | 0.9688 | likely_pathogenic | 0.9738 | pathogenic | -1.886 | Destabilizing | 0.999 | D | 0.812 | deleterious | None | None | None | None | N |
| I/F | 0.4315 | ambiguous | 0.4522 | ambiguous | -1.386 | Destabilizing | 0.997 | D | 0.662 | prob.neutral | N | 0.468463544 | None | None | N |
| I/G | 0.9771 | likely_pathogenic | 0.9817 | pathogenic | -2.815 | Highly Destabilizing | 0.999 | D | 0.789 | deleterious | None | None | None | None | N |
| I/H | 0.9588 | likely_pathogenic | 0.966 | pathogenic | -2.033 | Highly Destabilizing | 1.0 | D | 0.807 | deleterious | None | None | None | None | N |
| I/K | 0.9179 | likely_pathogenic | 0.9345 | pathogenic | -1.711 | Destabilizing | 0.999 | D | 0.811 | deleterious | None | None | None | None | N |
| I/L | 0.2474 | likely_benign | 0.2727 | benign | -0.886 | Destabilizing | 0.787 | D | 0.353 | neutral | N | 0.451142529 | None | None | N |
| I/M | 0.2244 | likely_benign | 0.254 | benign | -0.728 | Destabilizing | 0.997 | D | 0.617 | neutral | N | 0.477110824 | None | None | N |
| I/N | 0.9197 | likely_pathogenic | 0.9352 | pathogenic | -1.892 | Destabilizing | 0.999 | D | 0.823 | deleterious | N | 0.495303984 | None | None | N |
| I/P | 0.9912 | likely_pathogenic | 0.9921 | pathogenic | -1.337 | Destabilizing | 0.999 | D | 0.821 | deleterious | None | None | None | None | N |
| I/Q | 0.9331 | likely_pathogenic | 0.9406 | pathogenic | -1.819 | Destabilizing | 0.999 | D | 0.803 | deleterious | None | None | None | None | N |
| I/R | 0.8934 | likely_pathogenic | 0.9129 | pathogenic | -1.357 | Destabilizing | 0.999 | D | 0.821 | deleterious | None | None | None | None | N |
| I/S | 0.8985 | likely_pathogenic | 0.9177 | pathogenic | -2.628 | Highly Destabilizing | 0.997 | D | 0.764 | deleterious | N | 0.493783047 | None | None | N |
| I/T | 0.7855 | likely_pathogenic | 0.8207 | pathogenic | -2.296 | Highly Destabilizing | 0.976 | D | 0.696 | prob.delet. | N | 0.460520144 | None | None | N |
| I/V | 0.0754 | likely_benign | 0.0834 | benign | -1.337 | Destabilizing | 0.188 | N | 0.151 | neutral | N | 0.44381518 | None | None | N |
| I/W | 0.9726 | likely_pathogenic | 0.9755 | pathogenic | -1.634 | Destabilizing | 1.0 | D | 0.727 | deleterious | None | None | None | None | N |
| I/Y | 0.8947 | likely_pathogenic | 0.9044 | pathogenic | -1.361 | Destabilizing | 0.999 | D | 0.694 | prob.delet. | 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.