Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 3062 | 9409;9410;9411 | chr2:178768135;178768134;178768133 | chr2:179632862;179632861;179632860 |
| N2AB | 3062 | 9409;9410;9411 | chr2:178768135;178768134;178768133 | chr2:179632862;179632861;179632860 |
| N2A | 3062 | 9409;9410;9411 | chr2:178768135;178768134;178768133 | chr2:179632862;179632861;179632860 |
| N2B | 3016 | 9271;9272;9273 | chr2:178768135;178768134;178768133 | chr2:179632862;179632861;179632860 |
| Novex-1 | 3016 | 9271;9272;9273 | chr2:178768135;178768134;178768133 | chr2:179632862;179632861;179632860 |
| Novex-2 | 3016 | 9271;9272;9273 | chr2:178768135;178768134;178768133 | chr2:179632862;179632861;179632860 |
| Novex-3 | 3062 | 9409;9410;9411 | chr2:178768135;178768134;178768133 | chr2:179632862;179632861;179632860 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/R | rs769821924  |
-0.185 | 0.64 | N | 0.261 | 0.168 | 0.3085936734 | gnomAD-2.1.1 | 1.99E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 4.42E-05 | 0 |
| K/R | rs769821924 |
-0.185 | 0.64 | N | 0.261 | 0.168 | 0.3085936734 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| K/R | rs769821924 |
-0.185 | 0.64 | N | 0.261 | 0.168 | 0.3085936734 | gnomAD-4.0.0 | 2.85012E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.81353E-05 | 0 | 1.60046E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/A | 0.9613 | likely_pathogenic | 0.9474 | pathogenic | -0.58 | Destabilizing | 0.998 | D | 0.62 | neutral | None | None | None | None | N |
| K/C | 0.9764 | likely_pathogenic | 0.9757 | pathogenic | -0.503 | Destabilizing | 1.0 | D | 0.703 | prob.neutral | None | None | None | None | N |
| K/D | 0.9771 | likely_pathogenic | 0.9672 | pathogenic | -0.376 | Destabilizing | 1.0 | D | 0.759 | deleterious | None | None | None | None | N |
| K/E | 0.8619 | likely_pathogenic | 0.8166 | pathogenic | -0.244 | Destabilizing | 0.996 | D | 0.548 | neutral | D | 0.544988942 | None | None | N |
| K/F | 0.9954 | likely_pathogenic | 0.9948 | pathogenic | -0.011 | Destabilizing | 1.0 | D | 0.695 | prob.neutral | None | None | None | None | N |
| K/G | 0.9616 | likely_pathogenic | 0.9481 | pathogenic | -0.98 | Destabilizing | 1.0 | D | 0.639 | neutral | None | None | None | None | N |
| K/H | 0.751 | likely_pathogenic | 0.7465 | pathogenic | -1.273 | Destabilizing | 1.0 | D | 0.731 | prob.delet. | None | None | None | None | N |
| K/I | 0.9681 | likely_pathogenic | 0.9613 | pathogenic | 0.474 | Stabilizing | 1.0 | D | 0.729 | prob.delet. | D | 0.59731999 | None | None | N |
| K/L | 0.9413 | likely_pathogenic | 0.9326 | pathogenic | 0.474 | Stabilizing | 1.0 | D | 0.639 | neutral | None | None | None | None | N |
| K/M | 0.9185 | likely_pathogenic | 0.8982 | pathogenic | 0.316 | Stabilizing | 1.0 | D | 0.734 | prob.delet. | None | None | None | None | N |
| K/N | 0.9261 | likely_pathogenic | 0.9031 | pathogenic | -0.694 | Destabilizing | 0.999 | D | 0.673 | neutral | D | 0.583966118 | None | None | N |
| K/P | 0.9931 | likely_pathogenic | 0.9913 | pathogenic | 0.153 | Stabilizing | 1.0 | D | 0.763 | deleterious | None | None | None | None | N |
| K/Q | 0.5627 | ambiguous | 0.5165 | ambiguous | -0.679 | Destabilizing | 0.999 | D | 0.665 | neutral | N | 0.494635489 | None | None | N |
| K/R | 0.1502 | likely_benign | 0.156 | benign | -0.885 | Destabilizing | 0.64 | D | 0.261 | neutral | N | 0.500624634 | None | None | N |
| K/S | 0.9499 | likely_pathogenic | 0.9278 | pathogenic | -1.255 | Destabilizing | 0.998 | D | 0.611 | neutral | None | None | None | None | N |
| K/T | 0.8443 | likely_pathogenic | 0.7849 | pathogenic | -0.92 | Destabilizing | 0.999 | D | 0.72 | prob.delet. | N | 0.509611535 | None | None | N |
| K/V | 0.9466 | likely_pathogenic | 0.9354 | pathogenic | 0.153 | Stabilizing | 1.0 | D | 0.731 | prob.delet. | None | None | None | None | N |
| K/W | 0.9865 | likely_pathogenic | 0.9865 | pathogenic | 0.064 | Stabilizing | 1.0 | D | 0.705 | prob.neutral | None | None | None | None | N |
| K/Y | 0.9761 | likely_pathogenic | 0.9751 | pathogenic | 0.301 | Stabilizing | 1.0 | D | 0.718 | 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.