Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27129 | 81610;81611;81612 | chr2:178564747;178564746;178564745 | chr2:179429474;179429473;179429472 |
| N2AB | 25488 | 76687;76688;76689 | chr2:178564747;178564746;178564745 | chr2:179429474;179429473;179429472 |
| N2A | 24561 | 73906;73907;73908 | chr2:178564747;178564746;178564745 | chr2:179429474;179429473;179429472 |
| N2B | 18064 | 54415;54416;54417 | chr2:178564747;178564746;178564745 | chr2:179429474;179429473;179429472 |
| Novex-1 | 18189 | 54790;54791;54792 | chr2:178564747;178564746;178564745 | chr2:179429474;179429473;179429472 |
| Novex-2 | 18256 | 54991;54992;54993 | chr2:178564747;178564746;178564745 | chr2:179429474;179429473;179429472 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/E | None | None | 0.767 | N | 0.275 | 0.091 | 0.146414634003 | gnomAD-4.0.0 | 6.84659E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99798E-07 | 0 | 0 |
| D/H | rs778910088  |
0.521 | 1.0 | N | 0.731 | 0.345 | 0.313518423057 | gnomAD-2.1.1 | 8.12E-06 | None | None | None | None | N | None | 0 | 5.85E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| D/H | rs778910088 |
0.521 | 1.0 | N | 0.731 | 0.345 | 0.313518423057 | gnomAD-4.0.0 | 3.18747E-06 | None | None | None | None | N | None | 0 | 4.5861E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.1997 | likely_benign | 0.2069 | benign | 0.144 | Stabilizing | 0.999 | D | 0.668 | neutral | N | 0.507571162 | None | None | N |
| D/C | 0.6166 | likely_pathogenic | 0.63 | pathogenic | -0.076 | Destabilizing | 1.0 | D | 0.727 | prob.delet. | None | None | None | None | N |
| D/E | 0.1326 | likely_benign | 0.1501 | benign | -0.496 | Destabilizing | 0.767 | D | 0.275 | neutral | N | 0.475266742 | None | None | N |
| D/F | 0.6358 | likely_pathogenic | 0.6786 | pathogenic | 0.803 | Stabilizing | 1.0 | D | 0.762 | deleterious | None | None | None | None | N |
| D/G | 0.1556 | likely_benign | 0.1566 | benign | -0.206 | Destabilizing | 0.998 | D | 0.689 | prob.neutral | N | 0.510880826 | None | None | N |
| D/H | 0.3614 | ambiguous | 0.3806 | ambiguous | 0.918 | Stabilizing | 1.0 | D | 0.731 | prob.delet. | N | 0.469558359 | None | None | N |
| D/I | 0.5215 | ambiguous | 0.5618 | ambiguous | 1.067 | Stabilizing | 1.0 | D | 0.79 | deleterious | None | None | None | None | N |
| D/K | 0.5007 | ambiguous | 0.5091 | ambiguous | 0.162 | Stabilizing | 0.999 | D | 0.699 | prob.neutral | None | None | None | None | N |
| D/L | 0.4812 | ambiguous | 0.5009 | ambiguous | 1.067 | Stabilizing | 1.0 | D | 0.779 | deleterious | None | None | None | None | N |
| D/M | 0.5924 | likely_pathogenic | 0.6405 | pathogenic | 1.072 | Stabilizing | 1.0 | D | 0.737 | prob.delet. | None | None | None | None | N |
| D/N | 0.1163 | likely_benign | 0.1257 | benign | -0.565 | Destabilizing | 0.999 | D | 0.631 | neutral | N | 0.465973507 | None | None | N |
| D/P | 0.9021 | likely_pathogenic | 0.8959 | pathogenic | 0.785 | Stabilizing | 1.0 | D | 0.764 | deleterious | None | None | None | None | N |
| D/Q | 0.3518 | ambiguous | 0.3856 | ambiguous | -0.372 | Destabilizing | 0.999 | D | 0.703 | prob.neutral | None | None | None | None | N |
| D/R | 0.5682 | likely_pathogenic | 0.5793 | pathogenic | 0.496 | Stabilizing | 0.999 | D | 0.753 | deleterious | None | None | None | None | N |
| D/S | 0.1499 | likely_benign | 0.1603 | benign | -0.745 | Destabilizing | 0.997 | D | 0.603 | neutral | None | None | None | None | N |
| D/T | 0.2574 | likely_benign | 0.2866 | benign | -0.429 | Destabilizing | 1.0 | D | 0.747 | deleterious | None | None | None | None | N |
| D/V | 0.3262 | likely_benign | 0.3497 | ambiguous | 0.785 | Stabilizing | 0.999 | D | 0.785 | deleterious | D | 0.522905974 | None | None | N |
| D/W | 0.9174 | likely_pathogenic | 0.9245 | pathogenic | 0.956 | Stabilizing | 1.0 | D | 0.739 | prob.delet. | None | None | None | None | N |
| D/Y | 0.2787 | likely_benign | 0.2919 | benign | 1.083 | Stabilizing | 1.0 | D | 0.761 | deleterious | N | 0.485180625 | 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.