Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25705 | 77338;77339;77340 | chr2:178569019;178569018;178569017 | chr2:179433746;179433745;179433744 |
| N2AB | 24064 | 72415;72416;72417 | chr2:178569019;178569018;178569017 | chr2:179433746;179433745;179433744 |
| N2A | 23137 | 69634;69635;69636 | chr2:178569019;178569018;178569017 | chr2:179433746;179433745;179433744 |
| N2B | 16640 | 50143;50144;50145 | chr2:178569019;178569018;178569017 | chr2:179433746;179433745;179433744 |
| Novex-1 | 16765 | 50518;50519;50520 | chr2:178569019;178569018;178569017 | chr2:179433746;179433745;179433744 |
| Novex-2 | 16832 | 50719;50720;50721 | chr2:178569019;178569018;178569017 | chr2:179433746;179433745;179433744 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/T | rs561858074  |
-2.746 | 0.634 | N | 0.699 | 0.438 | 0.672566338644 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 6.56E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/T | rs561858074 |
-2.746 | 0.634 | N | 0.699 | 0.438 | 0.672566338644 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 1.4E-03 | None | None | 0 | 0 | None | None | None | 0 | None |
| I/T | rs561858074 |
-2.746 | 0.634 | N | 0.699 | 0.438 | 0.672566338644 | gnomAD-4.0.0 | 6.57583E-06 | None | None | None | None | N | None | 0 | 6.5505E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.9426 | likely_pathogenic | 0.9181 | pathogenic | -2.295 | Highly Destabilizing | 0.759 | D | 0.648 | neutral | None | None | None | None | N |
| I/C | 0.9538 | likely_pathogenic | 0.9388 | pathogenic | -1.669 | Destabilizing | 0.998 | D | 0.678 | prob.neutral | None | None | None | None | N |
| I/D | 0.9963 | likely_pathogenic | 0.9944 | pathogenic | -2.203 | Highly Destabilizing | 1.0 | D | 0.768 | deleterious | None | None | None | None | N |
| I/E | 0.9921 | likely_pathogenic | 0.9886 | pathogenic | -2.03 | Highly Destabilizing | 0.999 | D | 0.749 | deleterious | None | None | None | None | N |
| I/F | 0.6595 | likely_pathogenic | 0.5539 | ambiguous | -1.407 | Destabilizing | 0.932 | D | 0.755 | deleterious | None | None | None | None | N |
| I/G | 0.9856 | likely_pathogenic | 0.9796 | pathogenic | -2.802 | Highly Destabilizing | 0.982 | D | 0.753 | deleterious | None | None | None | None | N |
| I/H | 0.9927 | likely_pathogenic | 0.9884 | pathogenic | -2.233 | Highly Destabilizing | 0.996 | D | 0.757 | deleterious | None | None | None | None | N |
| I/K | 0.9873 | likely_pathogenic | 0.9809 | pathogenic | -1.689 | Destabilizing | 0.974 | D | 0.752 | deleterious | N | 0.495032901 | None | None | N |
| I/L | 0.1924 | likely_benign | 0.1526 | benign | -0.865 | Destabilizing | None | N | 0.259 | neutral | N | 0.372861945 | None | None | N |
| I/M | 0.2502 | likely_benign | 0.2009 | benign | -0.822 | Destabilizing | 0.282 | N | 0.669 | neutral | D | 0.522175255 | None | None | N |
| I/N | 0.9497 | likely_pathogenic | 0.9267 | pathogenic | -1.859 | Destabilizing | 1.0 | D | 0.771 | deleterious | None | None | None | None | N |
| I/P | 0.9723 | likely_pathogenic | 0.9646 | pathogenic | -1.318 | Destabilizing | 1.0 | D | 0.771 | deleterious | None | None | None | None | N |
| I/Q | 0.9887 | likely_pathogenic | 0.9831 | pathogenic | -1.792 | Destabilizing | 1.0 | D | 0.767 | deleterious | None | None | None | None | N |
| I/R | 0.9853 | likely_pathogenic | 0.9774 | pathogenic | -1.371 | Destabilizing | 0.998 | D | 0.771 | deleterious | N | 0.483676596 | None | None | N |
| I/S | 0.9695 | likely_pathogenic | 0.9542 | pathogenic | -2.597 | Highly Destabilizing | 0.982 | D | 0.725 | prob.delet. | None | None | None | None | N |
| I/T | 0.9467 | likely_pathogenic | 0.9225 | pathogenic | -2.279 | Highly Destabilizing | 0.634 | D | 0.699 | prob.neutral | N | 0.483169617 | None | None | N |
| I/V | 0.1315 | likely_benign | 0.1247 | benign | -1.318 | Destabilizing | None | N | 0.194 | neutral | N | 0.388028973 | None | None | N |
| I/W | 0.989 | likely_pathogenic | 0.9819 | pathogenic | -1.722 | Destabilizing | 0.999 | D | 0.762 | deleterious | None | None | None | None | N |
| I/Y | 0.9549 | likely_pathogenic | 0.9343 | pathogenic | -1.427 | Destabilizing | 0.717 | D | 0.729 | 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.