Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24447 | 73564;73565;73566 | chr2:178572793;178572792;178572791 | chr2:179437520;179437519;179437518 |
| N2AB | 22806 | 68641;68642;68643 | chr2:178572793;178572792;178572791 | chr2:179437520;179437519;179437518 |
| N2A | 21879 | 65860;65861;65862 | chr2:178572793;178572792;178572791 | chr2:179437520;179437519;179437518 |
| N2B | 15382 | 46369;46370;46371 | chr2:178572793;178572792;178572791 | chr2:179437520;179437519;179437518 |
| Novex-1 | 15507 | 46744;46745;46746 | chr2:178572793;178572792;178572791 | chr2:179437520;179437519;179437518 |
| Novex-2 | 15574 | 46945;46946;46947 | chr2:178572793;178572792;178572791 | chr2:179437520;179437519;179437518 |
| 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/K | rs377190830  |
-0.275 | 0.997 | N | 0.523 | 0.233 | None | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 6.46E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| R/K | rs377190830 |
-0.275 | 0.997 | N | 0.523 | 0.233 | None | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 7.24E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/K | rs377190830 |
-0.275 | 0.997 | N | 0.523 | 0.233 | None | gnomAD-4.0.0 | 5.57846E-06 | None | None | None | None | N | None | 1.06852E-04 | 0 | None | 0 | 0 | None | 0 | 0 | 8.47738E-07 | 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 | 0.9756 | likely_pathogenic | 0.9798 | pathogenic | -0.379 | Destabilizing | 0.999 | D | 0.606 | neutral | None | None | None | None | N |
| R/C | 0.6908 | likely_pathogenic | 0.7231 | pathogenic | -0.593 | Destabilizing | 1.0 | D | 0.737 | prob.delet. | None | None | None | None | N |
| R/D | 0.9849 | likely_pathogenic | 0.9878 | pathogenic | 0.047 | Stabilizing | 1.0 | D | 0.707 | prob.neutral | None | None | None | None | N |
| R/E | 0.8994 | likely_pathogenic | 0.9148 | pathogenic | 0.163 | Stabilizing | 0.999 | D | 0.629 | neutral | None | None | None | None | N |
| R/F | 0.9792 | likely_pathogenic | 0.9803 | pathogenic | -0.375 | Destabilizing | 1.0 | D | 0.728 | prob.delet. | None | None | None | None | N |
| R/G | 0.9578 | likely_pathogenic | 0.9627 | pathogenic | -0.642 | Destabilizing | 1.0 | D | 0.662 | neutral | N | 0.487634663 | None | None | N |
| R/H | 0.3297 | likely_benign | 0.3298 | benign | -0.99 | Destabilizing | 1.0 | D | 0.748 | deleterious | None | None | None | None | N |
| R/I | 0.9228 | likely_pathogenic | 0.9322 | pathogenic | 0.306 | Stabilizing | 1.0 | D | 0.721 | prob.delet. | N | 0.471617095 | None | None | N |
| R/K | 0.4368 | ambiguous | 0.4552 | ambiguous | -0.35 | Destabilizing | 0.997 | D | 0.523 | neutral | N | 0.451778094 | None | None | N |
| R/L | 0.8902 | likely_pathogenic | 0.8961 | pathogenic | 0.306 | Stabilizing | 1.0 | D | 0.662 | neutral | None | None | None | None | N |
| R/M | 0.9273 | likely_pathogenic | 0.9346 | pathogenic | -0.236 | Destabilizing | 1.0 | D | 0.741 | deleterious | None | None | None | None | N |
| R/N | 0.9606 | likely_pathogenic | 0.9659 | pathogenic | -0.185 | Destabilizing | 1.0 | D | 0.719 | prob.delet. | None | None | None | None | N |
| R/P | 0.9929 | likely_pathogenic | 0.9939 | pathogenic | 0.099 | Stabilizing | 1.0 | D | 0.703 | prob.neutral | None | None | None | None | N |
| R/Q | 0.3609 | ambiguous | 0.3868 | ambiguous | -0.238 | Destabilizing | 1.0 | D | 0.715 | prob.delet. | None | None | None | None | N |
| R/S | 0.9589 | likely_pathogenic | 0.9652 | pathogenic | -0.755 | Destabilizing | 1.0 | D | 0.703 | prob.neutral | N | 0.460767769 | None | None | N |
| R/T | 0.9007 | likely_pathogenic | 0.9155 | pathogenic | -0.465 | Destabilizing | 1.0 | D | 0.699 | prob.neutral | N | 0.446659078 | None | None | N |
| R/V | 0.9345 | likely_pathogenic | 0.9453 | pathogenic | 0.099 | Stabilizing | 1.0 | D | 0.712 | prob.delet. | None | None | None | None | N |
| R/W | 0.7164 | likely_pathogenic | 0.7057 | pathogenic | -0.249 | Destabilizing | 1.0 | D | 0.737 | prob.delet. | None | None | None | None | N |
| R/Y | 0.8929 | likely_pathogenic | 0.9014 | pathogenic | 0.108 | Stabilizing | 1.0 | D | 0.73 | 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.