Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27254 | 81985;81986;81987 | chr2:178564372;178564371;178564370 | chr2:179429099;179429098;179429097 |
| N2AB | 25613 | 77062;77063;77064 | chr2:178564372;178564371;178564370 | chr2:179429099;179429098;179429097 |
| N2A | 24686 | 74281;74282;74283 | chr2:178564372;178564371;178564370 | chr2:179429099;179429098;179429097 |
| N2B | 18189 | 54790;54791;54792 | chr2:178564372;178564371;178564370 | chr2:179429099;179429098;179429097 |
| Novex-1 | 18314 | 55165;55166;55167 | chr2:178564372;178564371;178564370 | chr2:179429099;179429098;179429097 |
| Novex-2 | 18381 | 55366;55367;55368 | chr2:178564372;178564371;178564370 | chr2:179429099;179429098;179429097 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/L | rs958378883  |
-1.156 | None | N | 0.224 | 0.075 | 0.0401082797425 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| F/L | rs958378883 |
-1.156 | None | N | 0.224 | 0.075 | 0.0401082797425 | gnomAD-4.0.0 | 1.02638E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.69842E-06 | 4.63725E-05 | 1.32534E-04 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/A | 0.3427 | ambiguous | 0.3803 | ambiguous | -1.576 | Destabilizing | 0.007 | N | 0.474 | neutral | None | None | None | None | N |
| F/C | 0.167 | likely_benign | 0.1773 | benign | -0.766 | Destabilizing | None | N | 0.473 | neutral | N | 0.456835697 | None | None | N |
| F/D | 0.677 | likely_pathogenic | 0.7101 | pathogenic | 0.498 | Stabilizing | 0.072 | N | 0.619 | neutral | None | None | None | None | N |
| F/E | 0.7265 | likely_pathogenic | 0.7546 | pathogenic | 0.522 | Stabilizing | 0.072 | N | 0.617 | neutral | None | None | None | None | N |
| F/G | 0.6573 | likely_pathogenic | 0.6958 | pathogenic | -1.838 | Destabilizing | 0.072 | N | 0.545 | neutral | None | None | None | None | N |
| F/H | 0.3949 | ambiguous | 0.4358 | ambiguous | -0.248 | Destabilizing | 0.628 | D | 0.559 | neutral | None | None | None | None | N |
| F/I | 0.0667 | likely_benign | 0.067 | benign | -0.85 | Destabilizing | 0.012 | N | 0.35 | neutral | N | 0.417181231 | None | None | N |
| F/K | 0.6955 | likely_pathogenic | 0.7265 | pathogenic | -0.522 | Destabilizing | 0.072 | N | 0.587 | neutral | None | None | None | None | N |
| F/L | 0.3243 | likely_benign | 0.4154 | ambiguous | -0.85 | Destabilizing | None | N | 0.224 | neutral | N | 0.429051663 | None | None | N |
| F/M | 0.2053 | likely_benign | 0.2504 | benign | -0.643 | Destabilizing | 0.12 | N | 0.551 | neutral | None | None | None | None | N |
| F/N | 0.4438 | ambiguous | 0.4811 | ambiguous | -0.429 | Destabilizing | 0.214 | N | 0.627 | neutral | None | None | None | None | N |
| F/P | 0.774 | likely_pathogenic | 0.8434 | pathogenic | -1.077 | Destabilizing | 0.356 | N | 0.623 | neutral | None | None | None | None | N |
| F/Q | 0.5651 | likely_pathogenic | 0.6298 | pathogenic | -0.499 | Destabilizing | 0.356 | N | 0.621 | neutral | None | None | None | None | N |
| F/R | 0.5955 | likely_pathogenic | 0.6324 | pathogenic | 0.055 | Stabilizing | 0.356 | N | 0.623 | neutral | None | None | None | None | N |
| F/S | 0.2924 | likely_benign | 0.2989 | benign | -1.29 | Destabilizing | 0.002 | N | 0.459 | neutral | N | 0.407580313 | None | None | N |
| F/T | 0.2473 | likely_benign | 0.2683 | benign | -1.169 | Destabilizing | 0.016 | N | 0.524 | neutral | None | None | None | None | N |
| F/V | 0.0762 | likely_benign | 0.0789 | benign | -1.077 | Destabilizing | None | N | 0.328 | neutral | N | 0.424280562 | None | None | N |
| F/W | 0.3192 | likely_benign | 0.3566 | ambiguous | -0.389 | Destabilizing | 0.864 | D | 0.571 | neutral | None | None | None | None | N |
| F/Y | 0.116 | likely_benign | 0.1258 | benign | -0.47 | Destabilizing | 0.106 | N | 0.457 | neutral | N | 0.481269995 | 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.