Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18872 | 56839;56840;56841 | chr2:178599179;178599178;178599177 | chr2:179463906;179463905;179463904 |
| N2AB | 17231 | 51916;51917;51918 | chr2:178599179;178599178;178599177 | chr2:179463906;179463905;179463904 |
| N2A | 16304 | 49135;49136;49137 | chr2:178599179;178599178;178599177 | chr2:179463906;179463905;179463904 |
| N2B | 9807 | 29644;29645;29646 | chr2:178599179;178599178;178599177 | chr2:179463906;179463905;179463904 |
| Novex-1 | 9932 | 30019;30020;30021 | chr2:178599179;178599178;178599177 | chr2:179463906;179463905;179463904 |
| Novex-2 | 9999 | 30220;30221;30222 | chr2:178599179;178599178;178599177 | chr2:179463906;179463905;179463904 |
| 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/N | rs747911018  |
-0.084 | 0.991 | N | 0.559 | 0.264 | 0.434384183301 | gnomAD-2.1.1 | 4.05E-05 | None | None | None | None | N | None | 0 | 3.56017E-04 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| D/N | rs747911018 |
-0.084 | 0.991 | N | 0.559 | 0.264 | 0.434384183301 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 2.41E-05 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 4.77555E-04 |
| D/N | rs747911018 |
-0.084 | 0.991 | N | 0.559 | 0.264 | 0.434384183301 | gnomAD-4.0.0 | 1.25722E-05 | None | None | None | None | N | None | 1.40087E-05 | 2.31406E-04 | None | 0 | 0 | None | 0 | 0 | 8.81447E-07 | 0 | 1.2059E-04 |
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 | 0.2734 | likely_benign | 0.2411 | benign | -0.29 | Destabilizing | 0.688 | D | 0.551 | neutral | N | 0.494476939 | None | None | N |
| D/C | 0.6826 | likely_pathogenic | 0.6494 | pathogenic | -0.181 | Destabilizing | 0.998 | D | 0.669 | prob.neutral | None | None | None | None | N |
| D/E | 0.1929 | likely_benign | 0.1689 | benign | -0.476 | Destabilizing | 0.971 | D | 0.526 | neutral | N | 0.400969346 | None | None | N |
| D/F | 0.5765 | likely_pathogenic | 0.5318 | ambiguous | 0.403 | Stabilizing | 0.925 | D | 0.679 | prob.neutral | None | None | None | None | N |
| D/G | 0.4452 | ambiguous | 0.4008 | ambiguous | -0.657 | Destabilizing | 0.971 | D | 0.557 | neutral | N | 0.521740898 | None | None | N |
| D/H | 0.4137 | ambiguous | 0.3676 | ambiguous | 0.298 | Stabilizing | 0.949 | D | 0.603 | neutral | N | 0.489668552 | None | None | N |
| D/I | 0.2846 | likely_benign | 0.2366 | benign | 0.679 | Stabilizing | 0.78 | D | 0.609 | neutral | None | None | None | None | N |
| D/K | 0.5892 | likely_pathogenic | 0.5055 | ambiguous | -0.077 | Destabilizing | 0.935 | D | 0.647 | neutral | None | None | None | None | N |
| D/L | 0.3547 | ambiguous | 0.2952 | benign | 0.679 | Stabilizing | 0.022 | N | 0.424 | neutral | None | None | None | None | N |
| D/M | 0.6064 | likely_pathogenic | 0.5372 | ambiguous | 0.895 | Stabilizing | 0.961 | D | 0.69 | prob.delet. | None | None | None | None | N |
| D/N | 0.177 | likely_benign | 0.1508 | benign | -0.742 | Destabilizing | 0.991 | D | 0.559 | neutral | N | 0.50765688 | None | None | N |
| D/P | 0.7421 | likely_pathogenic | 0.7193 | pathogenic | 0.382 | Stabilizing | 0.994 | D | 0.649 | prob.neutral | None | None | None | None | N |
| D/Q | 0.4499 | ambiguous | 0.3904 | ambiguous | -0.564 | Destabilizing | 0.994 | D | 0.584 | neutral | None | None | None | None | N |
| D/R | 0.6348 | likely_pathogenic | 0.5609 | ambiguous | 0.209 | Stabilizing | 0.981 | D | 0.697 | prob.delet. | None | None | None | None | N |
| D/S | 0.2382 | likely_benign | 0.2016 | benign | -0.944 | Destabilizing | 0.935 | D | 0.484 | neutral | None | None | None | None | N |
| D/T | 0.2936 | likely_benign | 0.2494 | benign | -0.629 | Destabilizing | 0.876 | D | 0.557 | neutral | None | None | None | None | N |
| D/V | 0.1788 | likely_benign | 0.1501 | benign | 0.382 | Stabilizing | 0.067 | N | 0.418 | neutral | N | 0.456286698 | None | None | N |
| D/W | 0.8834 | likely_pathogenic | 0.8736 | pathogenic | 0.646 | Stabilizing | 0.995 | D | 0.676 | prob.neutral | None | None | None | None | N |
| D/Y | 0.2451 | likely_benign | 0.2252 | benign | 0.678 | Stabilizing | 0.067 | N | 0.383 | neutral | N | 0.465618257 | 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.