Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1112 | 3559;3560;3561 | chr2:178782258;178782257;178782256 | chr2:179646985;179646984;179646983 |
| N2AB | 1112 | 3559;3560;3561 | chr2:178782258;178782257;178782256 | chr2:179646985;179646984;179646983 |
| N2A | 1112 | 3559;3560;3561 | chr2:178782258;178782257;178782256 | chr2:179646985;179646984;179646983 |
| N2B | 1066 | 3421;3422;3423 | chr2:178782258;178782257;178782256 | chr2:179646985;179646984;179646983 |
| Novex-1 | 1066 | 3421;3422;3423 | chr2:178782258;178782257;178782256 | chr2:179646985;179646984;179646983 |
| Novex-2 | 1066 | 3421;3422;3423 | chr2:178782258;178782257;178782256 | chr2:179646985;179646984;179646983 |
| Novex-3 | 1112 | 3559;3560;3561 | chr2:178782258;178782257;178782256 | chr2:179646985;179646984;179646983 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| H/L | rs540783675  |
0.675 | 1.0 | N | 0.718 | 0.584 | 0.682004838343 | gnomAD-2.1.1 | 3.98E-06 | None | None | None | None | N | None | 6.15E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| H/L | rs540783675 |
0.675 | 1.0 | N | 0.718 | 0.584 | 0.682004838343 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| H/L | rs540783675 |
0.675 | 1.0 | N | 0.718 | 0.584 | 0.682004838343 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 8E-04 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| H/L | rs540783675 |
0.675 | 1.0 | N | 0.718 | 0.584 | 0.682004838343 | gnomAD-4.0.0 | 6.56797E-06 | None | None | None | None | N | None | 2.40628E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| H/R | None | None | 1.0 | N | 0.663 | 0.499 | 0.294918367191 | gnomAD-4.0.0 | 1.59051E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43271E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| H/A | 0.6583 | likely_pathogenic | 0.6772 | pathogenic | -0.609 | Destabilizing | 0.999 | D | 0.635 | neutral | None | None | None | None | N |
| H/C | 0.6234 | likely_pathogenic | 0.5913 | pathogenic | 0.184 | Stabilizing | 1.0 | D | 0.756 | deleterious | None | None | None | None | N |
| H/D | 0.7086 | likely_pathogenic | 0.7196 | pathogenic | -0.866 | Destabilizing | 1.0 | D | 0.707 | prob.neutral | N | 0.439202125 | None | None | N |
| H/E | 0.7415 | likely_pathogenic | 0.7437 | pathogenic | -0.754 | Destabilizing | 0.999 | D | 0.571 | neutral | None | None | None | None | N |
| H/F | 0.5238 | ambiguous | 0.5289 | ambiguous | 0.818 | Stabilizing | 1.0 | D | 0.745 | deleterious | None | None | None | None | N |
| H/G | 0.8119 | likely_pathogenic | 0.8275 | pathogenic | -0.976 | Destabilizing | 0.999 | D | 0.65 | neutral | None | None | None | None | N |
| H/I | 0.6171 | likely_pathogenic | 0.6229 | pathogenic | 0.415 | Stabilizing | 1.0 | D | 0.755 | deleterious | None | None | None | None | N |
| H/K | 0.718 | likely_pathogenic | 0.7005 | pathogenic | -0.387 | Destabilizing | 1.0 | D | 0.702 | prob.neutral | None | None | None | None | N |
| H/L | 0.3094 | likely_benign | 0.3219 | benign | 0.415 | Stabilizing | 1.0 | D | 0.718 | prob.delet. | N | 0.462531608 | None | None | N |
| H/M | 0.7382 | likely_pathogenic | 0.7555 | pathogenic | 0.157 | Stabilizing | 1.0 | D | 0.733 | prob.delet. | None | None | None | None | N |
| H/N | 0.2804 | likely_benign | 0.3025 | benign | -0.715 | Destabilizing | 0.999 | D | 0.561 | neutral | N | 0.408338544 | None | None | N |
| H/P | 0.8107 | likely_pathogenic | 0.8349 | pathogenic | 0.093 | Stabilizing | 1.0 | D | 0.742 | deleterious | N | 0.508190801 | None | None | N |
| H/Q | 0.4991 | ambiguous | 0.5181 | ambiguous | -0.476 | Destabilizing | 1.0 | D | 0.669 | neutral | N | 0.381740347 | None | None | N |
| H/R | 0.4422 | ambiguous | 0.4115 | ambiguous | -0.962 | Destabilizing | 1.0 | D | 0.663 | neutral | N | 0.43211158 | None | None | N |
| H/S | 0.5135 | ambiguous | 0.5373 | ambiguous | -0.588 | Destabilizing | 1.0 | D | 0.702 | prob.neutral | None | None | None | None | N |
| H/T | 0.6319 | likely_pathogenic | 0.6497 | pathogenic | -0.367 | Destabilizing | 1.0 | D | 0.733 | prob.delet. | None | None | None | None | N |
| H/V | 0.5445 | ambiguous | 0.5529 | ambiguous | 0.093 | Stabilizing | 1.0 | D | 0.749 | deleterious | None | None | None | None | N |
| H/W | 0.6913 | likely_pathogenic | 0.682 | pathogenic | 1.139 | Stabilizing | 1.0 | D | 0.757 | deleterious | None | None | None | None | N |
| H/Y | 0.235 | likely_benign | 0.2256 | benign | 1.111 | Stabilizing | 0.999 | D | 0.571 | neutral | N | 0.500245546 | 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.