Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31783 | 95572;95573;95574 | chr2:178545889;178545888;178545887 | chr2:179410616;179410615;179410614 |
| N2AB | 30142 | 90649;90650;90651 | chr2:178545889;178545888;178545887 | chr2:179410616;179410615;179410614 |
| N2A | 29215 | 87868;87869;87870 | chr2:178545889;178545888;178545887 | chr2:179410616;179410615;179410614 |
| N2B | 22718 | 68377;68378;68379 | chr2:178545889;178545888;178545887 | chr2:179410616;179410615;179410614 |
| Novex-1 | 22843 | 68752;68753;68754 | chr2:178545889;178545888;178545887 | chr2:179410616;179410615;179410614 |
| Novex-2 | 22910 | 68953;68954;68955 | chr2:178545889;178545888;178545887 | chr2:179410616;179410615;179410614 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/T | rs1696869417  |
None | 0.638 | N | 0.667 | 0.348 | 0.311387274539 | 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 |
| R/T | rs1696869417 |
None | 0.638 | N | 0.667 | 0.348 | 0.311387274539 | gnomAD-4.0.0 | 2.02984E-06 | None | None | None | None | N | None | 1.74709E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.2049E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.648 | likely_pathogenic | 0.6409 | pathogenic | -1.3 | Destabilizing | 0.25 | N | 0.629 | neutral | None | None | None | None | N |
| R/C | 0.1911 | likely_benign | 0.1849 | benign | -1.28 | Destabilizing | 0.982 | D | 0.713 | prob.delet. | None | None | None | None | N |
| R/D | 0.9321 | likely_pathogenic | 0.9306 | pathogenic | -0.356 | Destabilizing | 0.7 | D | 0.705 | prob.neutral | None | None | None | None | N |
| R/E | 0.6859 | likely_pathogenic | 0.6858 | pathogenic | -0.174 | Destabilizing | 0.25 | N | 0.644 | neutral | None | None | None | None | N |
| R/F | 0.7329 | likely_pathogenic | 0.7464 | pathogenic | -0.706 | Destabilizing | 0.935 | D | 0.746 | deleterious | None | None | None | None | N |
| R/G | 0.553 | ambiguous | 0.5424 | ambiguous | -1.669 | Destabilizing | 0.334 | N | 0.69 | prob.neutral | N | 0.508377443 | None | None | N |
| R/H | 0.1753 | likely_benign | 0.1715 | benign | -1.692 | Destabilizing | 0.826 | D | 0.689 | prob.neutral | None | None | None | None | N |
| R/I | 0.486 | ambiguous | 0.5166 | ambiguous | -0.268 | Destabilizing | 0.826 | D | 0.744 | deleterious | None | None | None | None | N |
| R/K | 0.1795 | likely_benign | 0.1575 | benign | -1.204 | Destabilizing | 0.002 | N | 0.337 | neutral | N | 0.502279985 | None | None | N |
| R/L | 0.4141 | ambiguous | 0.4492 | ambiguous | -0.268 | Destabilizing | 0.399 | N | 0.69 | prob.neutral | None | None | None | None | N |
| R/M | 0.3799 | ambiguous | 0.397 | ambiguous | -0.7 | Destabilizing | 0.976 | D | 0.672 | neutral | N | 0.46547661 | None | None | N |
| R/N | 0.8108 | likely_pathogenic | 0.81 | pathogenic | -0.833 | Destabilizing | 0.7 | D | 0.661 | neutral | None | None | None | None | N |
| R/P | 0.9896 | likely_pathogenic | 0.9925 | pathogenic | -0.594 | Destabilizing | 0.826 | D | 0.719 | prob.delet. | None | None | None | None | N |
| R/Q | 0.1474 | likely_benign | 0.1471 | benign | -0.832 | Destabilizing | 0.539 | D | 0.663 | neutral | None | None | None | None | N |
| R/S | 0.6301 | likely_pathogenic | 0.6358 | pathogenic | -1.696 | Destabilizing | 0.201 | N | 0.648 | neutral | N | 0.435788421 | None | None | N |
| R/T | 0.3845 | ambiguous | 0.3969 | ambiguous | -1.305 | Destabilizing | 0.638 | D | 0.667 | neutral | N | 0.481520711 | None | None | N |
| R/V | 0.526 | ambiguous | 0.5555 | ambiguous | -0.594 | Destabilizing | 0.7 | D | 0.732 | prob.delet. | None | None | None | None | N |
| R/W | 0.2978 | likely_benign | 0.3283 | benign | -0.233 | Destabilizing | 0.976 | D | 0.664 | neutral | N | 0.520405312 | None | None | N |
| R/Y | 0.5754 | likely_pathogenic | 0.5749 | pathogenic | -0.021 | Destabilizing | 0.935 | D | 0.724 | prob.delet. | 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.