Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29569 | 88930;88931;88932 | chr2:178554642;178554641;178554640 | chr2:179419369;179419368;179419367 |
| N2AB | 27928 | 84007;84008;84009 | chr2:178554642;178554641;178554640 | chr2:179419369;179419368;179419367 |
| N2A | 27001 | 81226;81227;81228 | chr2:178554642;178554641;178554640 | chr2:179419369;179419368;179419367 |
| N2B | 20504 | 61735;61736;61737 | chr2:178554642;178554641;178554640 | chr2:179419369;179419368;179419367 |
| Novex-1 | 20629 | 62110;62111;62112 | chr2:178554642;178554641;178554640 | chr2:179419369;179419368;179419367 |
| Novex-2 | 20696 | 62311;62312;62313 | chr2:178554642;178554641;178554640 | chr2:179419369;179419368;179419367 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/C | None | None | 0.999 | D | 0.807 | 0.751 | 0.797327051344 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.66327E-05 |
| Y/F | None | None | 0.067 | D | 0.459 | 0.574 | 0.49590494691 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| Y/N | rs199821241  |
-3.478 | 0.998 | D | 0.829 | 0.863 | None | gnomAD-2.1.1 | 2.01E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 4.44E-05 | 0 |
| Y/N | rs199821241 |
-3.478 | 0.998 | D | 0.829 | 0.863 | None | 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 |
| Y/N | rs199821241 |
-3.478 | 0.998 | D | 0.829 | 0.863 | None | gnomAD-4.0.0 | 1.54913E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.1189E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/A | 0.9955 | likely_pathogenic | 0.9954 | pathogenic | -3.785 | Highly Destabilizing | 0.968 | D | 0.782 | deleterious | None | None | None | None | N |
| Y/C | 0.8685 | likely_pathogenic | 0.8793 | pathogenic | -2.28 | Highly Destabilizing | 0.999 | D | 0.807 | deleterious | D | 0.643047426 | None | None | N |
| Y/D | 0.9957 | likely_pathogenic | 0.9949 | pathogenic | -3.971 | Highly Destabilizing | 0.998 | D | 0.849 | deleterious | D | 0.643451034 | None | None | N |
| Y/E | 0.9989 | likely_pathogenic | 0.9988 | pathogenic | -3.787 | Highly Destabilizing | 0.998 | D | 0.833 | deleterious | None | None | None | None | N |
| Y/F | 0.1856 | likely_benign | 0.2281 | benign | -1.733 | Destabilizing | 0.067 | N | 0.459 | neutral | D | 0.568958336 | None | None | N |
| Y/G | 0.9896 | likely_pathogenic | 0.9891 | pathogenic | -4.126 | Highly Destabilizing | 0.995 | D | 0.845 | deleterious | None | None | None | None | N |
| Y/H | 0.954 | likely_pathogenic | 0.954 | pathogenic | -2.772 | Highly Destabilizing | 0.998 | D | 0.733 | prob.delet. | D | 0.643047426 | None | None | N |
| Y/I | 0.9689 | likely_pathogenic | 0.9675 | pathogenic | -2.602 | Highly Destabilizing | 0.982 | D | 0.757 | deleterious | None | None | None | None | N |
| Y/K | 0.9982 | likely_pathogenic | 0.9978 | pathogenic | -2.882 | Highly Destabilizing | 0.995 | D | 0.834 | deleterious | None | None | None | None | N |
| Y/L | 0.9448 | likely_pathogenic | 0.9307 | pathogenic | -2.602 | Highly Destabilizing | 0.938 | D | 0.712 | prob.delet. | None | None | None | None | N |
| Y/M | 0.9792 | likely_pathogenic | 0.9798 | pathogenic | -2.269 | Highly Destabilizing | 0.999 | D | 0.771 | deleterious | None | None | None | None | N |
| Y/N | 0.9726 | likely_pathogenic | 0.9712 | pathogenic | -3.574 | Highly Destabilizing | 0.998 | D | 0.829 | deleterious | D | 0.643451034 | None | None | N |
| Y/P | 0.9993 | likely_pathogenic | 0.9992 | pathogenic | -3.017 | Highly Destabilizing | 0.998 | D | 0.861 | deleterious | None | None | None | None | N |
| Y/Q | 0.997 | likely_pathogenic | 0.9971 | pathogenic | -3.368 | Highly Destabilizing | 0.998 | D | 0.765 | deleterious | None | None | None | None | N |
| Y/R | 0.9921 | likely_pathogenic | 0.9911 | pathogenic | -2.504 | Highly Destabilizing | 0.995 | D | 0.824 | deleterious | None | None | None | None | N |
| Y/S | 0.9825 | likely_pathogenic | 0.9814 | pathogenic | -3.858 | Highly Destabilizing | 0.994 | D | 0.827 | deleterious | D | 0.643451034 | None | None | N |
| Y/T | 0.9931 | likely_pathogenic | 0.9925 | pathogenic | -3.58 | Highly Destabilizing | 0.995 | D | 0.829 | deleterious | None | None | None | None | N |
| Y/V | 0.9478 | likely_pathogenic | 0.9427 | pathogenic | -3.017 | Highly Destabilizing | 0.968 | D | 0.746 | deleterious | None | None | None | None | N |
| Y/W | 0.8276 | likely_pathogenic | 0.8569 | pathogenic | -1.025 | Destabilizing | 1.0 | D | 0.727 | 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.