Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20298 | 61117;61118;61119 | chr2:178590833;178590832;178590831 | chr2:179455560;179455559;179455558 |
| N2AB | 18657 | 56194;56195;56196 | chr2:178590833;178590832;178590831 | chr2:179455560;179455559;179455558 |
| N2A | 17730 | 53413;53414;53415 | chr2:178590833;178590832;178590831 | chr2:179455560;179455559;179455558 |
| N2B | 11233 | 33922;33923;33924 | chr2:178590833;178590832;178590831 | chr2:179455560;179455559;179455558 |
| Novex-1 | 11358 | 34297;34298;34299 | chr2:178590833;178590832;178590831 | chr2:179455560;179455559;179455558 |
| Novex-2 | 11425 | 34498;34499;34500 | chr2:178590833;178590832;178590831 | chr2:179455560;179455559;179455558 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/G | None | None | 1.0 | N | 0.722 | 0.546 | 0.508815697893 | gnomAD-4.0.0 | 6.87291E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.03847E-07 | 0 | 0 |
| D/Y | rs780008017  |
-0.535 | 1.0 | D | 0.715 | 0.477 | 0.799971844007 | gnomAD-2.1.1 | 8.07E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.92E-06 | 1.665E-04 |
| D/Y | rs780008017 |
-0.535 | 1.0 | D | 0.715 | 0.477 | 0.799971844007 | gnomAD-4.0.0 | 3.21642E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.80646E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.7879 | likely_pathogenic | 0.8329 | pathogenic | -0.449 | Destabilizing | 1.0 | D | 0.755 | deleterious | N | 0.493057892 | None | None | I |
| D/C | 0.9549 | likely_pathogenic | 0.9618 | pathogenic | 0.178 | Stabilizing | 1.0 | D | 0.714 | prob.delet. | None | None | None | None | I |
| D/E | 0.8335 | likely_pathogenic | 0.8548 | pathogenic | -0.407 | Destabilizing | 1.0 | D | 0.443 | neutral | N | 0.485625152 | None | None | I |
| D/F | 0.9736 | likely_pathogenic | 0.9777 | pathogenic | -0.646 | Destabilizing | 1.0 | D | 0.734 | prob.delet. | None | None | None | None | I |
| D/G | 0.75 | likely_pathogenic | 0.7819 | pathogenic | -0.655 | Destabilizing | 1.0 | D | 0.722 | prob.delet. | N | 0.510378906 | None | None | I |
| D/H | 0.8563 | likely_pathogenic | 0.8794 | pathogenic | -0.877 | Destabilizing | 1.0 | D | 0.707 | prob.neutral | N | 0.514391377 | None | None | I |
| D/I | 0.9444 | likely_pathogenic | 0.9569 | pathogenic | 0.054 | Stabilizing | 1.0 | D | 0.761 | deleterious | None | None | None | None | I |
| D/K | 0.9353 | likely_pathogenic | 0.9488 | pathogenic | 0.284 | Stabilizing | 1.0 | D | 0.776 | deleterious | None | None | None | None | I |
| D/L | 0.933 | likely_pathogenic | 0.9443 | pathogenic | 0.054 | Stabilizing | 1.0 | D | 0.77 | deleterious | None | None | None | None | I |
| D/M | 0.9705 | likely_pathogenic | 0.9763 | pathogenic | 0.49 | Stabilizing | 1.0 | D | 0.707 | prob.neutral | None | None | None | None | I |
| D/N | 0.1801 | likely_benign | 0.1726 | benign | 0.03 | Stabilizing | 1.0 | D | 0.702 | prob.neutral | N | 0.505264362 | None | None | I |
| D/P | 0.9626 | likely_pathogenic | 0.9703 | pathogenic | -0.092 | Destabilizing | 1.0 | D | 0.782 | deleterious | None | None | None | None | I |
| D/Q | 0.9253 | likely_pathogenic | 0.9399 | pathogenic | 0.054 | Stabilizing | 1.0 | D | 0.752 | deleterious | None | None | None | None | I |
| D/R | 0.9287 | likely_pathogenic | 0.9456 | pathogenic | 0.175 | Stabilizing | 1.0 | D | 0.778 | deleterious | None | None | None | None | I |
| D/S | 0.4015 | ambiguous | 0.4309 | ambiguous | -0.088 | Destabilizing | 1.0 | D | 0.718 | prob.delet. | None | None | None | None | I |
| D/T | 0.6038 | likely_pathogenic | 0.6301 | pathogenic | 0.081 | Stabilizing | 1.0 | D | 0.781 | deleterious | None | None | None | None | I |
| D/V | 0.8499 | likely_pathogenic | 0.8826 | pathogenic | -0.092 | Destabilizing | 1.0 | D | 0.775 | deleterious | N | 0.509111458 | None | None | I |
| D/W | 0.9942 | likely_pathogenic | 0.9955 | pathogenic | -0.571 | Destabilizing | 1.0 | D | 0.704 | prob.neutral | None | None | None | None | I |
| D/Y | 0.825 | likely_pathogenic | 0.8591 | pathogenic | -0.42 | Destabilizing | 1.0 | D | 0.715 | prob.delet. | D | 0.544612406 | 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.