Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 34943 | 105052;105053;105054 | chr2:178531788;178531787;178531786 | chr2:179396515;179396514;179396513 |
| N2AB | 33302 | 100129;100130;100131 | chr2:178531788;178531787;178531786 | chr2:179396515;179396514;179396513 |
| N2A | 32375 | 97348;97349;97350 | chr2:178531788;178531787;178531786 | chr2:179396515;179396514;179396513 |
| N2B | 25878 | 77857;77858;77859 | chr2:178531788;178531787;178531786 | chr2:179396515;179396514;179396513 |
| Novex-1 | 26003 | 78232;78233;78234 | chr2:178531788;178531787;178531786 | chr2:179396515;179396514;179396513 |
| Novex-2 | 26070 | 78433;78434;78435 | chr2:178531788;178531787;178531786 | chr2:179396515;179396514;179396513 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/Q | rs780707238  |
-0.166 | 1.0 | N | 0.739 | 0.421 | 0.338592109245 | gnomAD-2.1.1 | 8.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 6.54E-05 | None | 0 | 0 | 0 |
| R/Q | rs780707238 |
-0.166 | 1.0 | N | 0.739 | 0.421 | 0.338592109245 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/Q | rs780707238 |
-0.166 | 1.0 | N | 0.739 | 0.421 | 0.338592109245 | gnomAD-4.0.0 | 5.57671E-06 | None | None | None | None | N | None | 2.66937E-05 | 0 | None | 0 | 6.68211E-05 | None | 0 | 0 | 1.6951E-06 | 2.19568E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.8804 | likely_pathogenic | 0.8657 | pathogenic | -0.154 | Destabilizing | 0.999 | D | 0.596 | neutral | None | None | None | None | N |
| R/C | 0.5674 | likely_pathogenic | 0.5465 | ambiguous | -0.296 | Destabilizing | 1.0 | D | 0.763 | deleterious | None | None | None | None | N |
| R/D | 0.9678 | likely_pathogenic | 0.9644 | pathogenic | -0.096 | Destabilizing | 1.0 | D | 0.715 | prob.delet. | None | None | None | None | N |
| R/E | 0.8269 | likely_pathogenic | 0.8217 | pathogenic | -0.018 | Destabilizing | 0.999 | D | 0.645 | neutral | None | None | None | None | N |
| R/F | 0.9087 | likely_pathogenic | 0.9193 | pathogenic | -0.287 | Destabilizing | 1.0 | D | 0.727 | prob.delet. | None | None | None | None | N |
| R/G | 0.8488 | likely_pathogenic | 0.8297 | pathogenic | -0.379 | Destabilizing | 1.0 | D | 0.635 | neutral | N | 0.484010943 | None | None | N |
| R/H | 0.2438 | likely_benign | 0.2424 | benign | -0.825 | Destabilizing | 1.0 | D | 0.767 | deleterious | None | None | None | None | N |
| R/I | 0.7415 | likely_pathogenic | 0.7524 | pathogenic | 0.413 | Stabilizing | 1.0 | D | 0.736 | prob.delet. | None | None | None | None | N |
| R/K | 0.2836 | likely_benign | 0.2887 | benign | -0.258 | Destabilizing | 0.998 | D | 0.494 | neutral | None | None | None | None | N |
| R/L | 0.6845 | likely_pathogenic | 0.6789 | pathogenic | 0.413 | Stabilizing | 1.0 | D | 0.635 | neutral | N | 0.484010943 | None | None | N |
| R/M | 0.8111 | likely_pathogenic | 0.792 | pathogenic | -0.016 | Destabilizing | 1.0 | D | 0.747 | deleterious | None | None | None | None | N |
| R/N | 0.9144 | likely_pathogenic | 0.9165 | pathogenic | 0.02 | Stabilizing | 1.0 | D | 0.754 | deleterious | None | None | None | None | N |
| R/P | 0.9897 | likely_pathogenic | 0.9845 | pathogenic | 0.245 | Stabilizing | 1.0 | D | 0.703 | prob.neutral | N | 0.488872788 | None | None | N |
| R/Q | 0.2681 | likely_benign | 0.2664 | benign | -0.094 | Destabilizing | 1.0 | D | 0.739 | prob.delet. | N | 0.51479907 | None | None | N |
| R/S | 0.891 | likely_pathogenic | 0.8846 | pathogenic | -0.41 | Destabilizing | 1.0 | D | 0.719 | prob.delet. | None | None | None | None | N |
| R/T | 0.7727 | likely_pathogenic | 0.7681 | pathogenic | -0.185 | Destabilizing | 1.0 | D | 0.713 | prob.delet. | None | None | None | None | N |
| R/V | 0.7446 | likely_pathogenic | 0.7589 | pathogenic | 0.245 | Stabilizing | 1.0 | D | 0.717 | prob.delet. | None | None | None | None | N |
| R/W | 0.6231 | likely_pathogenic | 0.622 | pathogenic | -0.252 | Destabilizing | 1.0 | D | 0.778 | deleterious | None | None | None | None | N |
| R/Y | 0.8122 | likely_pathogenic | 0.8188 | pathogenic | 0.133 | Stabilizing | 1.0 | D | 0.734 | 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.