Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19318 | 58177;58178;58179 | chr2:178594542;178594541;178594540 | chr2:179459269;179459268;179459267 |
| N2AB | 17677 | 53254;53255;53256 | chr2:178594542;178594541;178594540 | chr2:179459269;179459268;179459267 |
| N2A | 16750 | 50473;50474;50475 | chr2:178594542;178594541;178594540 | chr2:179459269;179459268;179459267 |
| N2B | 10253 | 30982;30983;30984 | chr2:178594542;178594541;178594540 | chr2:179459269;179459268;179459267 |
| Novex-1 | 10378 | 31357;31358;31359 | chr2:178594542;178594541;178594540 | chr2:179459269;179459268;179459267 |
| Novex-2 | 10445 | 31558;31559;31560 | chr2:178594542;178594541;178594540 | chr2:179459269;179459268;179459267 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/K | rs756463146  |
-0.062 | 0.27 | N | 0.255 | 0.125 | 0.124217242631 | gnomAD-2.1.1 | 8.05E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.78E-05 | 0 |
| N/K | rs756463146 |
-0.062 | 0.27 | N | 0.255 | 0.125 | 0.124217242631 | gnomAD-4.0.0 | 1.64257E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.06925E-05 | 0 | 1.65684E-05 |
| N/T | rs767305625 |
-0.547 | 0.27 | N | 0.279 | 0.097 | 0.21279746466 | gnomAD-2.1.1 | 1.61E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.30804E-04 | None | 0 | 0 | 0 |
| N/T | rs767305625 |
-0.547 | 0.27 | N | 0.279 | 0.097 | 0.21279746466 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 4.14422E-04 | 0 |
| N/T | rs767305625 |
-0.547 | 0.27 | N | 0.279 | 0.097 | 0.21279746466 | gnomAD-4.0.0 | 1.4256E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.52647E-04 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/A | 0.3153 | likely_benign | 0.3026 | benign | -1.252 | Destabilizing | 0.013 | N | 0.379 | neutral | None | None | None | None | N |
| N/C | 0.2431 | likely_benign | 0.2502 | benign | -0.31 | Destabilizing | 0.981 | D | 0.604 | neutral | None | None | None | None | N |
| N/D | 0.2629 | likely_benign | 0.2381 | benign | -0.842 | Destabilizing | 0.27 | N | 0.282 | neutral | N | 0.451621878 | None | None | N |
| N/E | 0.607 | likely_pathogenic | 0.5934 | pathogenic | -0.636 | Destabilizing | 0.013 | N | 0.157 | neutral | None | None | None | None | N |
| N/F | 0.7184 | likely_pathogenic | 0.6917 | pathogenic | -0.667 | Destabilizing | 0.893 | D | 0.641 | neutral | None | None | None | None | N |
| N/G | 0.2352 | likely_benign | 0.2214 | benign | -1.657 | Destabilizing | 0.3 | N | 0.247 | neutral | None | None | None | None | N |
| N/H | 0.1075 | likely_benign | 0.1013 | benign | -0.862 | Destabilizing | 0.927 | D | 0.451 | neutral | N | 0.410679333 | None | None | N |
| N/I | 0.7511 | likely_pathogenic | 0.7123 | pathogenic | -0.166 | Destabilizing | 0.473 | N | 0.569 | neutral | N | 0.475210814 | None | None | N |
| N/K | 0.4717 | ambiguous | 0.4064 | ambiguous | -0.071 | Destabilizing | 0.27 | N | 0.255 | neutral | N | 0.428686304 | None | None | N |
| N/L | 0.5191 | ambiguous | 0.495 | ambiguous | -0.166 | Destabilizing | 0.069 | N | 0.483 | neutral | None | None | None | None | N |
| N/M | 0.5634 | ambiguous | 0.5472 | ambiguous | 0.069 | Stabilizing | 0.037 | N | 0.395 | neutral | None | None | None | None | N |
| N/P | 0.9775 | likely_pathogenic | 0.9771 | pathogenic | -0.501 | Destabilizing | 0.828 | D | 0.592 | neutral | None | None | None | None | N |
| N/Q | 0.3822 | ambiguous | 0.3704 | ambiguous | -0.669 | Destabilizing | 0.085 | N | 0.169 | neutral | None | None | None | None | N |
| N/R | 0.4193 | ambiguous | 0.3825 | ambiguous | -0.11 | Destabilizing | 0.495 | N | 0.345 | neutral | None | None | None | None | N |
| N/S | 0.0744 | likely_benign | 0.0735 | benign | -1.084 | Destabilizing | 0.01 | N | 0.079 | neutral | N | 0.383164658 | None | None | N |
| N/T | 0.2255 | likely_benign | 0.22 | benign | -0.664 | Destabilizing | 0.27 | N | 0.279 | neutral | N | 0.441751602 | None | None | N |
| N/V | 0.6706 | likely_pathogenic | 0.6554 | pathogenic | -0.501 | Destabilizing | 0.329 | N | 0.493 | neutral | None | None | None | None | N |
| N/W | 0.8416 | likely_pathogenic | 0.8272 | pathogenic | -0.312 | Destabilizing | 0.995 | D | 0.623 | neutral | None | None | None | None | N |
| N/Y | 0.2688 | likely_benign | 0.2331 | benign | -0.081 | Destabilizing | 0.927 | D | 0.605 | neutral | N | 0.438327294 | 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.