Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24282 | 73069;73070;73071 | chr2:178573288;178573287;178573286 | chr2:179438015;179438014;179438013 |
| N2AB | 22641 | 68146;68147;68148 | chr2:178573288;178573287;178573286 | chr2:179438015;179438014;179438013 |
| N2A | 21714 | 65365;65366;65367 | chr2:178573288;178573287;178573286 | chr2:179438015;179438014;179438013 |
| N2B | 15217 | 45874;45875;45876 | chr2:178573288;178573287;178573286 | chr2:179438015;179438014;179438013 |
| Novex-1 | 15342 | 46249;46250;46251 | chr2:178573288;178573287;178573286 | chr2:179438015;179438014;179438013 |
| Novex-2 | 15409 | 46450;46451;46452 | chr2:178573288;178573287;178573286 | chr2:179438015;179438014;179438013 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/H | rs369711272  |
-1.316 | 0.741 | N | 0.451 | 0.384 | None | gnomAD-2.1.1 | 1.74E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 4.86E-05 | 2.81E-05 | 0 |
| Y/H | rs369711272 |
-1.316 | 0.741 | N | 0.451 | 0.384 | None | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| Y/H | rs369711272 |
-1.316 | 0.741 | N | 0.451 | 0.384 | None | gnomAD-4.0.0 | 8.80585E-06 | None | None | None | None | N | None | 0 | 3.56544E-05 | None | 0 | 0 | None | 1.57858E-05 | 0 | 9.41473E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/A | 0.6837 | likely_pathogenic | 0.6349 | pathogenic | -2.325 | Highly Destabilizing | 0.149 | N | 0.531 | neutral | None | None | None | None | N |
| Y/C | 0.1049 | likely_benign | 0.0876 | benign | -1.268 | Destabilizing | 0.915 | D | 0.611 | neutral | N | 0.485622596 | None | None | N |
| Y/D | 0.8162 | likely_pathogenic | 0.7631 | pathogenic | -2.017 | Highly Destabilizing | 0.741 | D | 0.624 | neutral | D | 0.526334022 | None | None | N |
| Y/E | 0.865 | likely_pathogenic | 0.83 | pathogenic | -1.87 | Destabilizing | 0.555 | D | 0.578 | neutral | None | None | None | None | N |
| Y/F | 0.0689 | likely_benign | 0.0665 | benign | -0.763 | Destabilizing | None | N | 0.158 | neutral | N | 0.424534065 | None | None | N |
| Y/G | 0.6612 | likely_pathogenic | 0.6082 | pathogenic | -2.685 | Highly Destabilizing | 0.262 | N | 0.609 | neutral | None | None | None | None | N |
| Y/H | 0.2846 | likely_benign | 0.25 | benign | -1.166 | Destabilizing | 0.741 | D | 0.451 | neutral | N | 0.475032997 | None | None | N |
| Y/I | 0.4592 | ambiguous | 0.41 | ambiguous | -1.187 | Destabilizing | 0.081 | N | 0.471 | neutral | None | None | None | None | N |
| Y/K | 0.8158 | likely_pathogenic | 0.7801 | pathogenic | -1.78 | Destabilizing | 0.555 | D | 0.58 | neutral | None | None | None | None | N |
| Y/L | 0.3377 | likely_benign | 0.3001 | benign | -1.187 | Destabilizing | 0.001 | N | 0.294 | neutral | None | None | None | None | N |
| Y/M | 0.5185 | ambiguous | 0.4829 | ambiguous | -0.889 | Destabilizing | 0.38 | N | 0.521 | neutral | None | None | None | None | N |
| Y/N | 0.5079 | ambiguous | 0.4327 | ambiguous | -2.431 | Highly Destabilizing | 0.741 | D | 0.597 | neutral | D | 0.526080532 | None | None | N |
| Y/P | 0.9887 | likely_pathogenic | 0.981 | pathogenic | -1.569 | Destabilizing | 0.791 | D | 0.646 | neutral | None | None | None | None | N |
| Y/Q | 0.6565 | likely_pathogenic | 0.6031 | pathogenic | -2.225 | Highly Destabilizing | 0.791 | D | 0.525 | neutral | None | None | None | None | N |
| Y/R | 0.7207 | likely_pathogenic | 0.6748 | pathogenic | -1.488 | Destabilizing | 0.555 | D | 0.594 | neutral | None | None | None | None | N |
| Y/S | 0.502 | ambiguous | 0.4372 | ambiguous | -2.801 | Highly Destabilizing | 0.211 | N | 0.575 | neutral | N | 0.478262227 | None | None | N |
| Y/T | 0.6964 | likely_pathogenic | 0.653 | pathogenic | -2.549 | Highly Destabilizing | 0.262 | N | 0.575 | neutral | None | None | None | None | N |
| Y/V | 0.3714 | ambiguous | 0.3346 | benign | -1.569 | Destabilizing | 0.081 | N | 0.487 | neutral | None | None | None | None | N |
| Y/W | 0.441 | ambiguous | 0.4082 | ambiguous | -0.309 | Destabilizing | 0.555 | D | 0.453 | 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.