Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27739 | 83440;83441;83442 | chr2:178562917;178562916;178562915 | chr2:179427644;179427643;179427642 |
| N2AB | 26098 | 78517;78518;78519 | chr2:178562917;178562916;178562915 | chr2:179427644;179427643;179427642 |
| N2A | 25171 | 75736;75737;75738 | chr2:178562917;178562916;178562915 | chr2:179427644;179427643;179427642 |
| N2B | 18674 | 56245;56246;56247 | chr2:178562917;178562916;178562915 | chr2:179427644;179427643;179427642 |
| Novex-1 | 18799 | 56620;56621;56622 | chr2:178562917;178562916;178562915 | chr2:179427644;179427643;179427642 |
| Novex-2 | 18866 | 56821;56822;56823 | chr2:178562917;178562916;178562915 | chr2:179427644;179427643;179427642 |
| 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/I | rs886042186  |
-0.246 | 0.983 | N | 0.553 | 0.383 | 0.374076547971 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | I | None | 1.14811E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| F/I | rs886042186 |
-0.246 | 0.983 | N | 0.553 | 0.383 | 0.374076547971 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| F/I | rs886042186 |
-0.246 | 0.983 | N | 0.553 | 0.383 | 0.374076547971 | gnomAD-4.0.0 | 7.43747E-06 | None | None | None | None | I | None | 1.33515E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 9.32423E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/A | 0.4495 | ambiguous | 0.4942 | ambiguous | -0.736 | Destabilizing | 0.916 | D | 0.475 | neutral | None | None | None | None | I |
| F/C | 0.3946 | ambiguous | 0.4831 | ambiguous | -0.323 | Destabilizing | 0.999 | D | 0.599 | neutral | N | 0.513061834 | None | None | I |
| F/D | 0.5073 | ambiguous | 0.5336 | ambiguous | 0.965 | Stabilizing | 0.033 | N | 0.413 | neutral | None | None | None | None | I |
| F/E | 0.6348 | likely_pathogenic | 0.6573 | pathogenic | 0.937 | Stabilizing | 0.95 | D | 0.523 | neutral | None | None | None | None | I |
| F/G | 0.6746 | likely_pathogenic | 0.6938 | pathogenic | -0.897 | Destabilizing | 0.975 | D | 0.523 | neutral | None | None | None | None | I |
| F/H | 0.4432 | ambiguous | 0.4684 | ambiguous | 0.271 | Stabilizing | 0.999 | D | 0.544 | neutral | None | None | None | None | I |
| F/I | 0.3417 | ambiguous | 0.4175 | ambiguous | -0.345 | Destabilizing | 0.983 | D | 0.553 | neutral | N | 0.502114122 | None | None | I |
| F/K | 0.7504 | likely_pathogenic | 0.7768 | pathogenic | 0.04 | Stabilizing | 0.975 | D | 0.624 | neutral | None | None | None | None | I |
| F/L | 0.8447 | likely_pathogenic | 0.8712 | pathogenic | -0.345 | Destabilizing | 0.944 | D | 0.533 | neutral | N | 0.430656668 | None | None | I |
| F/M | 0.4847 | ambiguous | 0.5154 | ambiguous | -0.306 | Destabilizing | 0.999 | D | 0.569 | neutral | None | None | None | None | I |
| F/N | 0.3276 | likely_benign | 0.3489 | ambiguous | 0.076 | Stabilizing | 0.95 | D | 0.629 | neutral | None | None | None | None | I |
| F/P | 0.9734 | likely_pathogenic | 0.9785 | pathogenic | -0.456 | Destabilizing | 0.987 | D | 0.628 | neutral | None | None | None | None | I |
| F/Q | 0.6224 | likely_pathogenic | 0.6387 | pathogenic | 0.058 | Stabilizing | 0.987 | D | 0.627 | neutral | None | None | None | None | I |
| F/R | 0.671 | likely_pathogenic | 0.7024 | pathogenic | 0.397 | Stabilizing | 0.987 | D | 0.627 | neutral | None | None | None | None | I |
| F/S | 0.2981 | likely_benign | 0.3279 | benign | -0.589 | Destabilizing | 0.967 | D | 0.46 | neutral | N | 0.421628966 | None | None | I |
| F/T | 0.3665 | ambiguous | 0.4125 | ambiguous | -0.525 | Destabilizing | 0.975 | D | 0.508 | neutral | None | None | None | None | I |
| F/V | 0.3131 | likely_benign | 0.381 | ambiguous | -0.456 | Destabilizing | 0.983 | D | 0.497 | neutral | N | 0.502114122 | None | None | I |
| F/W | 0.474 | ambiguous | 0.49 | ambiguous | -0.286 | Destabilizing | 0.999 | D | 0.574 | neutral | None | None | None | None | I |
| F/Y | 0.1104 | likely_benign | 0.1122 | benign | -0.225 | Destabilizing | 0.981 | D | 0.541 | neutral | N | 0.413321701 | None | None | I |
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.