Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 10083 | 30472;30473;30474 | chr2:178702640;178702639;178702638 | chr2:179567367;179567366;179567365 |
| N2AB | 9766 | 29521;29522;29523 | chr2:178702640;178702639;178702638 | chr2:179567367;179567366;179567365 |
| N2A | 8839 | 26740;26741;26742 | chr2:178702640;178702639;178702638 | chr2:179567367;179567366;179567365 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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/C | rs377714947  |
-0.466 | 0.999 | None | 0.547 | 0.443 | None | gnomAD-2.1.1 | 2.86E-05 | None | None | None | None | N | None | 1.23977E-04 | 0 | None | 0 | 5.12E-05 | None | 3.27E-05 | None | 0 | 2.34E-05 | 0 |
| R/C | rs377714947 |
-0.466 | 0.999 | None | 0.547 | 0.443 | None | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 1.92234E-04 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/C | rs377714947 |
-0.466 | 0.999 | None | 0.547 | 0.443 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 1E-03 | 0 | None | None | None | 0 | None |
| R/C | rs377714947 |
-0.466 | 0.999 | None | 0.547 | 0.443 | None | gnomAD-4.0.0 | 1.36336E-05 | None | None | None | None | N | None | 3.9984E-05 | 0 | None | 0 | 2.22826E-05 | None | 0 | 0 | 1.10203E-05 | 2.1965E-05 | 4.80231E-05 |
| R/H | rs759347532 |
-0.79 | 0.998 | None | 0.624 | 0.161 | None | gnomAD-2.1.1 | 7.14E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.56E-05 | 0 |
| R/H | rs759347532 |
-0.79 | 0.998 | None | 0.624 | 0.161 | None | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 4.41E-05 | 0 | 0 |
| R/H | rs759347532 |
-0.79 | 0.998 | None | 0.624 | 0.161 | None | gnomAD-4.0.0 | 2.41697E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.22697E-05 | None | 0 | 0 | 3.05162E-05 | 0 | 3.20236E-05 |
| R/L | rs759347532 |
0.539 | 0.837 | None | 0.566 | 0.252 | 0.573134939963 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.87E-06 | 0 |
| R/L | rs759347532 |
0.539 | 0.837 | None | 0.566 | 0.252 | 0.573134939963 | gnomAD-4.0.0 | 1.36852E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.7991E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.5117 | ambiguous | 0.6919 | pathogenic | -0.828 | Destabilizing | 0.525 | D | 0.467 | neutral | None | None | None | None | N |
| R/C | 0.406 | ambiguous | 0.5389 | ambiguous | -0.861 | Destabilizing | 0.999 | D | 0.547 | neutral | None | None | None | None | N |
| R/D | 0.8046 | likely_pathogenic | 0.871 | pathogenic | 0.142 | Stabilizing | 0.842 | D | 0.585 | neutral | None | None | None | None | N |
| R/E | 0.5135 | ambiguous | 0.6421 | pathogenic | 0.263 | Stabilizing | 0.842 | D | 0.594 | neutral | None | None | None | None | N |
| R/F | 0.8588 | likely_pathogenic | 0.9144 | pathogenic | -0.763 | Destabilizing | 0.974 | D | 0.567 | neutral | None | None | None | None | N |
| R/G | 0.3802 | ambiguous | 0.529 | ambiguous | -1.101 | Destabilizing | 0.837 | D | 0.593 | neutral | None | None | None | None | N |
| R/H | 0.1795 | likely_benign | 0.2005 | benign | -1.328 | Destabilizing | 0.998 | D | 0.624 | neutral | None | None | None | None | N |
| R/I | 0.5909 | likely_pathogenic | 0.7681 | pathogenic | -0.106 | Destabilizing | 0.728 | D | 0.579 | neutral | None | None | None | None | N |
| R/K | 0.1506 | likely_benign | 0.2114 | benign | -0.61 | Destabilizing | 0.688 | D | 0.561 | neutral | None | None | None | None | N |
| R/L | 0.4795 | ambiguous | 0.6062 | pathogenic | -0.106 | Destabilizing | 0.837 | D | 0.566 | neutral | None | None | None | None | N |
| R/M | 0.4797 | ambiguous | 0.6694 | pathogenic | -0.506 | Destabilizing | 0.974 | D | 0.584 | neutral | None | None | None | None | N |
| R/N | 0.6371 | likely_pathogenic | 0.762 | pathogenic | -0.248 | Destabilizing | 0.842 | D | 0.61 | neutral | None | None | None | None | N |
| R/P | 0.5931 | likely_pathogenic | 0.6424 | pathogenic | -0.327 | Destabilizing | 0.986 | D | 0.575 | neutral | None | None | None | None | N |
| R/Q | 0.1555 | likely_benign | 0.1963 | benign | -0.399 | Destabilizing | 0.974 | D | 0.639 | neutral | None | None | None | None | N |
| R/S | 0.5494 | ambiguous | 0.7343 | pathogenic | -1.054 | Destabilizing | 0.121 | N | 0.359 | neutral | None | None | None | None | N |
| R/T | 0.29 | likely_benign | 0.5133 | ambiguous | -0.755 | Destabilizing | 0.067 | N | 0.325 | neutral | None | None | None | None | N |
| R/V | 0.6112 | likely_pathogenic | 0.7784 | pathogenic | -0.327 | Destabilizing | 0.067 | N | 0.441 | neutral | None | None | None | None | N |
| R/W | 0.509 | ambiguous | 0.5822 | pathogenic | -0.47 | Destabilizing | 0.998 | D | 0.572 | neutral | None | None | None | None | N |
| R/Y | 0.7072 | likely_pathogenic | 0.7514 | pathogenic | -0.171 | Destabilizing | 0.991 | D | 0.574 | neutral | 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.