Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 7183 | 21772;21773;21774 | chr2:178723553;178723552;178723551 | chr2:179588280;179588279;179588278 |
| N2AB | 6866 | 20821;20822;20823 | chr2:178723553;178723552;178723551 | chr2:179588280;179588279;179588278 |
| N2A | 5939 | 18040;18041;18042 | chr2:178723553;178723552;178723551 | chr2:179588280;179588279;179588278 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| C/G | None | None | 0.98 | N | 0.688 | 0.502 | 0.802337023659 | gnomAD-4.0.0 | 1.59216E-06 | None | None | None | None | N | None | 5.66123E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| C/R | rs1295622488  |
-1.253 | 0.997 | N | 0.755 | 0.562 | 0.744421343069 | gnomAD-2.1.1 | 8.05E-06 | None | None | None | None | N | None | 0 | 5.81E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| C/R | rs1295622488 |
-1.253 | 0.997 | N | 0.755 | 0.562 | 0.744421343069 | gnomAD-4.0.0 | 3.18433E-06 | None | None | None | None | N | None | 0 | 4.57687E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| C/Y | rs189951108 |
-1.528 | 0.999 | N | 0.699 | 0.335 | None | gnomAD-2.1.1 | 3.86076E-04 | None | None | None | None | N | None | 1.65481E-04 | 4.82242E-04 | None | 0 | 0 | None | 1.96412E-04 | None | 4E-05 | 6.02052E-04 | 4.22654E-04 |
| C/Y | rs189951108 |
-1.528 | 0.999 | N | 0.699 | 0.335 | None | gnomAD-3.1.2 | 4.73342E-04 | None | None | None | None | N | None | 1.20668E-04 | 3.93236E-04 | 0 | 0 | 0 | None | 0 | 0 | 8.82405E-04 | 0 | 4.77555E-04 |
| C/Y | rs189951108 |
-1.528 | 0.999 | N | 0.699 | 0.335 | None | 1000 genomes | 9.98403E-04 | None | None | None | None | N | None | 0 | 1.4E-03 | None | None | 0 | 4E-03 | None | None | None | 0 | None |
| C/Y | rs189951108 |
-1.528 | 0.999 | N | 0.699 | 0.335 | None | gnomAD-4.0.0 | 7.21462E-04 | None | None | None | None | N | None | 1.06655E-04 | 5.50367E-04 | None | 0 | 0 | None | 0 | 0 | 9.03708E-04 | 3.51486E-04 | 4.00333E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| C/A | 0.587 | likely_pathogenic | 0.5989 | pathogenic | -1.839 | Destabilizing | 0.931 | D | 0.496 | neutral | None | None | None | None | N |
| C/D | 0.8214 | likely_pathogenic | 0.8475 | pathogenic | -0.82 | Destabilizing | 0.996 | D | 0.722 | prob.delet. | None | None | None | None | N |
| C/E | 0.8462 | likely_pathogenic | 0.8616 | pathogenic | -0.641 | Destabilizing | 0.996 | D | 0.739 | prob.delet. | None | None | None | None | N |
| C/F | 0.2787 | likely_benign | 0.3083 | benign | -1.07 | Destabilizing | 0.999 | D | 0.689 | prob.neutral | N | 0.474835173 | None | None | N |
| C/G | 0.2757 | likely_benign | 0.3008 | benign | -2.194 | Highly Destabilizing | 0.98 | D | 0.688 | prob.neutral | N | 0.482717042 | None | None | N |
| C/H | 0.5944 | likely_pathogenic | 0.6241 | pathogenic | -2.233 | Highly Destabilizing | 1.0 | D | 0.743 | deleterious | None | None | None | None | N |
| C/I | 0.5884 | likely_pathogenic | 0.6051 | pathogenic | -0.892 | Destabilizing | 0.998 | D | 0.655 | neutral | None | None | None | None | N |
| C/K | 0.8758 | likely_pathogenic | 0.8855 | pathogenic | -1.185 | Destabilizing | 0.996 | D | 0.721 | prob.delet. | None | None | None | None | N |
| C/L | 0.5849 | likely_pathogenic | 0.5972 | pathogenic | -0.892 | Destabilizing | 0.993 | D | 0.584 | neutral | None | None | None | None | N |
| C/M | 0.7063 | likely_pathogenic | 0.7206 | pathogenic | 0.131 | Stabilizing | 1.0 | D | 0.657 | neutral | None | None | None | None | N |
| C/N | 0.603 | likely_pathogenic | 0.6311 | pathogenic | -1.45 | Destabilizing | 0.996 | D | 0.742 | deleterious | None | None | None | None | N |
| C/P | 0.9635 | likely_pathogenic | 0.9715 | pathogenic | -1.183 | Destabilizing | 0.998 | D | 0.759 | deleterious | None | None | None | None | N |
| C/Q | 0.7044 | likely_pathogenic | 0.7242 | pathogenic | -1.154 | Destabilizing | 0.998 | D | 0.759 | deleterious | None | None | None | None | N |
| C/R | 0.5768 | likely_pathogenic | 0.6039 | pathogenic | -1.297 | Destabilizing | 0.997 | D | 0.755 | deleterious | N | 0.519474171 | None | None | N |
| C/S | 0.3998 | ambiguous | 0.4223 | ambiguous | -1.938 | Destabilizing | 0.659 | D | 0.419 | neutral | N | 0.517415301 | None | None | N |
| C/T | 0.5812 | likely_pathogenic | 0.5904 | pathogenic | -1.566 | Destabilizing | 0.971 | D | 0.61 | neutral | None | None | None | None | N |
| C/V | 0.5331 | ambiguous | 0.5372 | ambiguous | -1.183 | Destabilizing | 0.993 | D | 0.625 | neutral | None | None | None | None | N |
| C/W | 0.47 | ambiguous | 0.5146 | ambiguous | -1.23 | Destabilizing | 1.0 | D | 0.701 | prob.neutral | N | 0.489326861 | None | None | N |
| C/Y | 0.278 | likely_benign | 0.3065 | benign | -1.161 | Destabilizing | 0.999 | D | 0.699 | prob.neutral | N | 0.437778295 | 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.