Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32956 | 99091;99092;99093 | chr2:178539069;178539068;178539067 | chr2:179403796;179403795;179403794 |
| N2AB | 31315 | 94168;94169;94170 | chr2:178539069;178539068;178539067 | chr2:179403796;179403795;179403794 |
| N2A | 30388 | 91387;91388;91389 | chr2:178539069;178539068;178539067 | chr2:179403796;179403795;179403794 |
| N2B | 23891 | 71896;71897;71898 | chr2:178539069;178539068;178539067 | chr2:179403796;179403795;179403794 |
| Novex-1 | 24016 | 72271;72272;72273 | chr2:178539069;178539068;178539067 | chr2:179403796;179403795;179403794 |
| Novex-2 | 24083 | 72472;72473;72474 | chr2:178539069;178539068;178539067 | chr2:179403796;179403795;179403794 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/K | None | None | 0.994 | N | 0.659 | 0.457 | 0.638638447811 | gnomAD-4.0.0 | 6.8422E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.65662E-05 |
| M/R | None | None | 0.998 | N | 0.696 | 0.48 | 0.622465732353 | gnomAD-4.0.0 | 1.36844E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.799E-06 | 0 | 0 |
| M/T | rs727504962  |
None | 0.994 | N | 0.641 | 0.455 | 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 |
| M/T | rs727504962 |
None | 0.994 | N | 0.641 | 0.455 | None | gnomAD-4.0.0 | 9.2957E-06 | None | None | None | None | N | None | 1.33501E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.18671E-05 | 0 | 0 |
| M/V | rs727503538 |
-0.144 | 0.985 | N | 0.509 | 0.344 | 0.526539220858 | gnomAD-2.1.1 | 1.43E-05 | None | None | None | None | N | None | 8.26E-05 | 0 | None | 0 | 1.02459E-04 | None | 0 | None | 0 | 0 | 0 |
| M/V | rs727503538 |
-0.144 | 0.985 | N | 0.509 | 0.344 | 0.526539220858 | gnomAD-3.1.2 | 3.94E-05 | None | None | None | None | N | None | 7.24E-05 | 1.31096E-04 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 4.78011E-04 |
| M/V | rs727503538 |
-0.144 | 0.985 | N | 0.509 | 0.344 | 0.526539220858 | gnomAD-4.0.0 | 1.85901E-05 | None | None | None | None | N | None | 7.99659E-05 | 3.33378E-05 | None | 0 | 1.11448E-04 | None | 0 | 0 | 8.47659E-07 | 0 | 2.56082E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.5108 | ambiguous | 0.5394 | ambiguous | -0.832 | Destabilizing | 0.989 | D | 0.629 | neutral | None | None | None | None | N |
| M/C | 0.806 | likely_pathogenic | 0.8103 | pathogenic | -0.731 | Destabilizing | 1.0 | D | 0.723 | prob.delet. | None | None | None | None | N |
| M/D | 0.936 | likely_pathogenic | 0.9378 | pathogenic | 0.708 | Stabilizing | 0.999 | D | 0.742 | deleterious | None | None | None | None | N |
| M/E | 0.7308 | likely_pathogenic | 0.7246 | pathogenic | 0.738 | Stabilizing | 0.999 | D | 0.653 | neutral | None | None | None | None | N |
| M/F | 0.5691 | likely_pathogenic | 0.5753 | pathogenic | 0.034 | Stabilizing | 0.999 | D | 0.609 | neutral | None | None | None | None | N |
| M/G | 0.7827 | likely_pathogenic | 0.8101 | pathogenic | -1.122 | Destabilizing | 0.995 | D | 0.661 | neutral | None | None | None | None | N |
| M/H | 0.6932 | likely_pathogenic | 0.6893 | pathogenic | -0.146 | Destabilizing | 1.0 | D | 0.726 | prob.delet. | None | None | None | None | N |
| M/I | 0.6386 | likely_pathogenic | 0.6416 | pathogenic | -0.118 | Destabilizing | 0.985 | D | 0.592 | neutral | N | 0.445098551 | None | None | N |
| M/K | 0.5093 | ambiguous | 0.4831 | ambiguous | 0.307 | Stabilizing | 0.994 | D | 0.659 | neutral | N | 0.405713443 | None | None | N |
| M/L | 0.2448 | likely_benign | 0.2552 | benign | -0.118 | Destabilizing | 0.927 | D | 0.381 | neutral | N | 0.46674326 | None | None | N |
| M/N | 0.6549 | likely_pathogenic | 0.6863 | pathogenic | 0.328 | Stabilizing | 0.999 | D | 0.737 | prob.delet. | None | None | None | None | N |
| M/P | 0.9926 | likely_pathogenic | 0.9924 | pathogenic | -0.326 | Destabilizing | 0.999 | D | 0.736 | prob.delet. | None | None | None | None | N |
| M/Q | 0.3599 | ambiguous | 0.364 | ambiguous | 0.33 | Stabilizing | 0.999 | D | 0.613 | neutral | None | None | None | None | N |
| M/R | 0.51 | ambiguous | 0.4843 | ambiguous | 0.624 | Stabilizing | 0.998 | D | 0.696 | prob.neutral | N | 0.389954557 | None | None | N |
| M/S | 0.467 | ambiguous | 0.5033 | ambiguous | -0.329 | Destabilizing | 0.995 | D | 0.61 | neutral | None | None | None | None | N |
| M/T | 0.2881 | likely_benign | 0.3069 | benign | -0.171 | Destabilizing | 0.994 | D | 0.641 | neutral | N | 0.393493508 | None | None | N |
| M/V | 0.1449 | likely_benign | 0.1468 | benign | -0.326 | Destabilizing | 0.985 | D | 0.509 | neutral | N | 0.43397748 | None | None | N |
| M/W | 0.877 | likely_pathogenic | 0.8749 | pathogenic | 0.047 | Stabilizing | 1.0 | D | 0.721 | prob.delet. | None | None | None | None | N |
| M/Y | 0.7862 | likely_pathogenic | 0.7875 | pathogenic | 0.138 | Stabilizing | 0.999 | D | 0.733 | 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.