Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28384 | 85375;85376;85377 | chr2:178560982;178560981;178560980 | chr2:179425709;179425708;179425707 |
| N2AB | 26743 | 80452;80453;80454 | chr2:178560982;178560981;178560980 | chr2:179425709;179425708;179425707 |
| N2A | 25816 | 77671;77672;77673 | chr2:178560982;178560981;178560980 | chr2:179425709;179425708;179425707 |
| N2B | 19319 | 58180;58181;58182 | chr2:178560982;178560981;178560980 | chr2:179425709;179425708;179425707 |
| Novex-1 | 19444 | 58555;58556;58557 | chr2:178560982;178560981;178560980 | chr2:179425709;179425708;179425707 |
| Novex-2 | 19511 | 58756;58757;58758 | chr2:178560982;178560981;178560980 | chr2:179425709;179425708;179425707 |
| 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/Q | rs1465916943  |
0.207 | 0.999 | N | 0.626 | 0.305 | 0.317667799068 | gnomAD-2.1.1 | 8.05E-06 | None | None | None | None | I | None | 0 | 0 | None | 9.96E-05 | 0 | None | 0 | None | 0 | 8.91E-06 | 0 |
| R/Q | rs1465916943 |
0.207 | 0.999 | N | 0.626 | 0.305 | 0.317667799068 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | I | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/Q | rs1465916943 |
0.207 | 0.999 | N | 0.626 | 0.305 | 0.317667799068 | gnomAD-4.0.0 | 8.05636E-06 | None | None | None | None | I | None | 4.00545E-05 | 0 | None | 3.37861E-05 | 0 | None | 1.56265E-05 | 0 | 6.78089E-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 | 0.8057 | likely_pathogenic | 0.817 | pathogenic | 0.091 | Stabilizing | 0.845 | D | 0.612 | neutral | None | None | None | None | I |
| R/C | 0.2506 | likely_benign | 0.2776 | benign | -0.227 | Destabilizing | 0.999 | D | 0.698 | prob.neutral | None | None | None | None | I |
| R/D | 0.9491 | likely_pathogenic | 0.9522 | pathogenic | -0.311 | Destabilizing | 0.996 | D | 0.662 | neutral | None | None | None | None | I |
| R/E | 0.7119 | likely_pathogenic | 0.7307 | pathogenic | -0.268 | Destabilizing | 0.957 | D | 0.617 | neutral | None | None | None | None | I |
| R/F | 0.7444 | likely_pathogenic | 0.7595 | pathogenic | -0.238 | Destabilizing | 0.975 | D | 0.677 | prob.neutral | None | None | None | None | I |
| R/G | 0.7441 | likely_pathogenic | 0.751 | pathogenic | -0.047 | Destabilizing | 0.977 | D | 0.609 | neutral | N | 0.503570002 | None | None | I |
| R/H | 0.1352 | likely_benign | 0.1488 | benign | -0.588 | Destabilizing | 0.999 | D | 0.606 | neutral | None | None | None | None | I |
| R/I | 0.4195 | ambiguous | 0.4444 | ambiguous | 0.411 | Stabilizing | 0.845 | D | 0.622 | neutral | None | None | None | None | I |
| R/K | 0.1249 | likely_benign | 0.1373 | benign | -0.128 | Destabilizing | 0.901 | D | 0.507 | neutral | None | None | None | None | I |
| R/L | 0.4154 | ambiguous | 0.4294 | ambiguous | 0.411 | Stabilizing | 0.913 | D | 0.621 | neutral | N | 0.503659357 | None | None | I |
| R/M | 0.5087 | ambiguous | 0.5249 | ambiguous | -0.075 | Destabilizing | 0.987 | D | 0.619 | neutral | None | None | None | None | I |
| R/N | 0.8455 | likely_pathogenic | 0.8567 | pathogenic | -0.076 | Destabilizing | 0.996 | D | 0.608 | neutral | None | None | None | None | I |
| R/P | 0.9822 | likely_pathogenic | 0.983 | pathogenic | 0.322 | Stabilizing | 0.998 | D | 0.661 | neutral | N | 0.503823491 | None | None | I |
| R/Q | 0.1537 | likely_benign | 0.1585 | benign | -0.089 | Destabilizing | 0.999 | D | 0.626 | neutral | N | 0.507987741 | None | None | I |
| R/S | 0.821 | likely_pathogenic | 0.8284 | pathogenic | -0.217 | Destabilizing | 0.987 | D | 0.6 | neutral | None | None | None | None | I |
| R/T | 0.6221 | likely_pathogenic | 0.6341 | pathogenic | -0.067 | Destabilizing | 0.916 | D | 0.631 | neutral | None | None | None | None | I |
| R/V | 0.5659 | likely_pathogenic | 0.5932 | pathogenic | 0.322 | Stabilizing | 0.033 | N | 0.534 | neutral | None | None | None | None | I |
| R/W | 0.3326 | likely_benign | 0.354 | ambiguous | -0.448 | Destabilizing | 0.999 | D | 0.713 | prob.delet. | None | None | None | None | I |
| R/Y | 0.5398 | ambiguous | 0.5703 | pathogenic | -0.033 | Destabilizing | 0.987 | D | 0.67 | neutral | None | None | 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.