Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18554 | 55885;55886;55887 | chr2:178601337;178601336;178601335 | chr2:179466064;179466063;179466062 |
| N2AB | 16913 | 50962;50963;50964 | chr2:178601337;178601336;178601335 | chr2:179466064;179466063;179466062 |
| N2A | 15986 | 48181;48182;48183 | chr2:178601337;178601336;178601335 | chr2:179466064;179466063;179466062 |
| N2B | 9489 | 28690;28691;28692 | chr2:178601337;178601336;178601335 | chr2:179466064;179466063;179466062 |
| Novex-1 | 9614 | 29065;29066;29067 | chr2:178601337;178601336;178601335 | chr2:179466064;179466063;179466062 |
| Novex-2 | 9681 | 29266;29267;29268 | chr2:178601337;178601336;178601335 | chr2:179466064;179466063;179466062 |
| 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 | rs202126861  |
-0.983 | 0.998 | N | 0.629 | 0.22 | None | gnomAD-2.1.1 | 3.6E-05 | None | None | None | None | N | None | 1.24285E-04 | 2.85E-05 | None | 0 | 1.03918E-04 | None | 0 | None | 4.02E-05 | 2.36E-05 | 0 |
| R/Q | rs202126861 |
-0.983 | 0.998 | N | 0.629 | 0.22 | None | gnomAD-3.1.2 | 6.58E-05 | None | None | None | None | N | None | 1.44907E-04 | 0 | 0 | 0 | 3.89105E-04 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| R/Q | rs202126861 |
-0.983 | 0.998 | N | 0.629 | 0.22 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 1E-03 | 0 | None | None | None | 0 | None |
| R/Q | rs202126861 |
-0.983 | 0.998 | N | 0.629 | 0.22 | None | gnomAD-4.0.0 | 2.04979E-05 | None | None | None | None | N | None | 1.33547E-04 | 3.34549E-05 | None | 0 | 4.48672E-05 | None | 3.1292E-05 | 0 | 1.18903E-05 | 2.20751E-05 | 1.60442E-05 |
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 | 0.5226 | ambiguous | 0.4989 | ambiguous | -1.316 | Destabilizing | 0.91 | D | 0.631 | neutral | None | None | None | None | N |
| R/C | 0.1653 | likely_benign | 0.1493 | benign | -1.386 | Destabilizing | 0.999 | D | 0.759 | deleterious | None | None | None | None | N |
| R/D | 0.9459 | likely_pathogenic | 0.9425 | pathogenic | -0.675 | Destabilizing | 0.986 | D | 0.677 | prob.neutral | None | None | None | None | N |
| R/E | 0.6778 | likely_pathogenic | 0.6627 | pathogenic | -0.474 | Destabilizing | 0.953 | D | 0.633 | neutral | None | None | None | None | N |
| R/F | 0.6866 | likely_pathogenic | 0.7404 | pathogenic | -0.544 | Destabilizing | 0.993 | D | 0.781 | deleterious | None | None | None | None | N |
| R/G | 0.5294 | ambiguous | 0.485 | ambiguous | -1.68 | Destabilizing | 0.975 | D | 0.661 | neutral | N | 0.498831563 | None | None | N |
| R/H | 0.2237 | likely_benign | 0.2217 | benign | -1.683 | Destabilizing | 0.999 | D | 0.661 | neutral | None | None | None | None | N |
| R/I | 0.4672 | ambiguous | 0.4844 | ambiguous | -0.287 | Destabilizing | 0.986 | D | 0.759 | deleterious | None | None | None | None | N |
| R/K | 0.1641 | likely_benign | 0.1712 | benign | -1.226 | Destabilizing | 0.893 | D | 0.653 | neutral | None | None | None | None | N |
| R/L | 0.3264 | likely_benign | 0.3639 | ambiguous | -0.287 | Destabilizing | 0.951 | D | 0.648 | neutral | N | 0.502146699 | None | None | N |
| R/M | 0.313 | likely_benign | 0.355 | ambiguous | -0.809 | Destabilizing | 0.999 | D | 0.676 | prob.neutral | None | None | None | None | N |
| R/N | 0.835 | likely_pathogenic | 0.8377 | pathogenic | -1.108 | Destabilizing | 0.986 | D | 0.629 | neutral | None | None | None | None | N |
| R/P | 0.9931 | likely_pathogenic | 0.992 | pathogenic | -0.614 | Destabilizing | 0.996 | D | 0.719 | prob.delet. | N | 0.521962248 | None | None | N |
| R/Q | 0.1518 | likely_benign | 0.1402 | benign | -0.929 | Destabilizing | 0.998 | D | 0.629 | neutral | N | 0.521903109 | None | None | N |
| R/S | 0.584 | likely_pathogenic | 0.5856 | pathogenic | -1.832 | Destabilizing | 0.91 | D | 0.613 | neutral | None | None | None | None | N |
| R/T | 0.2954 | likely_benign | 0.3309 | benign | -1.426 | Destabilizing | 0.214 | N | 0.479 | neutral | None | None | None | None | N |
| R/V | 0.4782 | ambiguous | 0.4939 | ambiguous | -0.614 | Destabilizing | 0.973 | D | 0.717 | prob.delet. | None | None | None | None | N |
| R/W | 0.4066 | ambiguous | 0.4085 | ambiguous | -0.18 | Destabilizing | 0.999 | D | 0.733 | prob.delet. | None | None | None | None | N |
| R/Y | 0.5914 | likely_pathogenic | 0.6197 | pathogenic | 0.036 | Stabilizing | 0.998 | D | 0.736 | 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.