Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25164 | 75715;75716;75717 | chr2:178570642;178570641;178570640 | chr2:179435369;179435368;179435367 |
| N2AB | 23523 | 70792;70793;70794 | chr2:178570642;178570641;178570640 | chr2:179435369;179435368;179435367 |
| N2A | 22596 | 68011;68012;68013 | chr2:178570642;178570641;178570640 | chr2:179435369;179435368;179435367 |
| N2B | 16099 | 48520;48521;48522 | chr2:178570642;178570641;178570640 | chr2:179435369;179435368;179435367 |
| Novex-1 | 16224 | 48895;48896;48897 | chr2:178570642;178570641;178570640 | chr2:179435369;179435368;179435367 |
| Novex-2 | 16291 | 49096;49097;49098 | chr2:178570642;178570641;178570640 | chr2:179435369;179435368;179435367 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/N | rs192468365  |
0.079 | 0.312 | N | 0.166 | 0.172 | None | gnomAD-2.1.1 | 6.07E-05 | None | None | None | None | N | None | 4.13E-05 | 2.54828E-04 | None | 0 | 1.02944E-04 | None | 3.27E-05 | None | 0 | 2.34E-05 | 1.40528E-04 |
| D/N | rs192468365 |
0.079 | 0.312 | N | 0.166 | 0.172 | None | gnomAD-3.1.2 | 1.57824E-04 | None | None | None | None | N | None | 4.83E-05 | 1.31182E-03 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| D/N | rs192468365 |
0.079 | 0.312 | N | 0.166 | 0.172 | None | 1000 genomes | 5.99042E-04 | None | None | None | None | N | None | 0 | 4.3E-03 | None | None | 0 | 0 | None | None | None | 0 | None |
| D/N | rs192468365 |
0.079 | 0.312 | N | 0.166 | 0.172 | None | gnomAD-4.0.0 | 4.02865E-05 | None | None | None | None | N | None | 4.00064E-05 | 5.0025E-04 | None | 0 | 6.69792E-05 | None | 0 | 0 | 8.47744E-06 | 5.49016E-05 | 2.24151E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.1356 | likely_benign | 0.1382 | benign | -0.104 | Destabilizing | 0.565 | D | 0.392 | neutral | N | 0.453249805 | None | None | N |
| D/C | 0.6204 | likely_pathogenic | 0.6542 | pathogenic | -0.137 | Destabilizing | 0.996 | D | 0.583 | neutral | None | None | None | None | N |
| D/E | 0.1777 | likely_benign | 0.1632 | benign | -0.207 | Destabilizing | 0.008 | N | 0.179 | neutral | N | 0.452133715 | None | None | N |
| D/F | 0.629 | likely_pathogenic | 0.6503 | pathogenic | 0.248 | Stabilizing | 0.858 | D | 0.517 | neutral | None | None | None | None | N |
| D/G | 0.197 | likely_benign | 0.1934 | benign | -0.328 | Destabilizing | 0.722 | D | 0.324 | neutral | N | 0.458397843 | None | None | N |
| D/H | 0.3106 | likely_benign | 0.3225 | benign | 0.657 | Stabilizing | 0.959 | D | 0.345 | neutral | N | 0.476887469 | None | None | N |
| D/I | 0.2887 | likely_benign | 0.3031 | benign | 0.447 | Stabilizing | 0.923 | D | 0.515 | neutral | None | None | None | None | N |
| D/K | 0.3773 | ambiguous | 0.4019 | ambiguous | 0.506 | Stabilizing | 0.633 | D | 0.307 | neutral | None | None | None | None | N |
| D/L | 0.3301 | likely_benign | 0.3532 | ambiguous | 0.447 | Stabilizing | 0.858 | D | 0.496 | neutral | None | None | None | None | N |
| D/M | 0.567 | likely_pathogenic | 0.5735 | pathogenic | 0.315 | Stabilizing | 0.996 | D | 0.535 | neutral | None | None | None | None | N |
| D/N | 0.0995 | likely_benign | 0.0964 | benign | -0.118 | Destabilizing | 0.312 | N | 0.166 | neutral | N | 0.45922406 | None | None | N |
| D/P | 0.4372 | ambiguous | 0.4394 | ambiguous | 0.286 | Stabilizing | 0.961 | D | 0.334 | neutral | None | None | None | None | N |
| D/Q | 0.3708 | ambiguous | 0.3726 | ambiguous | -0.018 | Destabilizing | 0.858 | D | 0.303 | neutral | None | None | None | None | N |
| D/R | 0.4013 | ambiguous | 0.4277 | ambiguous | 0.807 | Stabilizing | 0.923 | D | 0.451 | neutral | None | None | None | None | N |
| D/S | 0.1249 | likely_benign | 0.1208 | benign | -0.184 | Destabilizing | 0.633 | D | 0.262 | neutral | None | None | None | None | N |
| D/T | 0.2184 | likely_benign | 0.2202 | benign | 0.018 | Stabilizing | 0.923 | D | 0.315 | neutral | None | None | None | None | N |
| D/V | 0.1739 | likely_benign | 0.1855 | benign | 0.286 | Stabilizing | 0.901 | D | 0.516 | neutral | N | 0.491384099 | None | None | N |
| D/W | 0.8985 | likely_pathogenic | 0.9136 | pathogenic | 0.439 | Stabilizing | 0.989 | D | 0.584 | neutral | None | None | None | None | N |
| D/Y | 0.2198 | likely_benign | 0.2465 | benign | 0.522 | Stabilizing | 0.046 | N | 0.385 | neutral | N | 0.50932377 | 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.