Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32531 | 97816;97817;97818 | chr2:178541486;178541485;178541484 | chr2:179406213;179406212;179406211 |
| N2AB | 30890 | 92893;92894;92895 | chr2:178541486;178541485;178541484 | chr2:179406213;179406212;179406211 |
| N2A | 29963 | 90112;90113;90114 | chr2:178541486;178541485;178541484 | chr2:179406213;179406212;179406211 |
| N2B | 23466 | 70621;70622;70623 | chr2:178541486;178541485;178541484 | chr2:179406213;179406212;179406211 |
| Novex-1 | 23591 | 70996;70997;70998 | chr2:178541486;178541485;178541484 | chr2:179406213;179406212;179406211 |
| Novex-2 | 23658 | 71197;71198;71199 | chr2:178541486;178541485;178541484 | chr2:179406213;179406212;179406211 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | rs1060500477  |
None | 0.517 | N | 0.639 | 0.379 | 0.529060795929 | gnomAD-4.0.0 | 1.59214E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85979E-06 | 0 | 0 |
| V/E | rs1060500477 |
-1.463 | 0.983 | N | 0.817 | 0.53 | 0.827132642323 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.89E-06 | 0 |
| V/E | rs1060500477 |
-1.463 | 0.983 | N | 0.817 | 0.53 | 0.827132642323 | gnomAD-4.0.0 | 1.59214E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85979E-06 | 0 | 0 |
| V/M | None | None | 0.901 | N | 0.652 | 0.383 | 0.414930877219 | gnomAD-4.0.0 | 2.40064E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.625E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.8216 | likely_pathogenic | 0.7573 | pathogenic | -1.391 | Destabilizing | 0.517 | D | 0.639 | neutral | N | 0.477942604 | None | None | I |
| V/C | 0.9346 | likely_pathogenic | 0.9091 | pathogenic | -1.109 | Destabilizing | 0.996 | D | 0.71 | prob.delet. | None | None | None | None | I |
| V/D | 0.9784 | likely_pathogenic | 0.9733 | pathogenic | -1.042 | Destabilizing | 0.987 | D | 0.838 | deleterious | None | None | None | None | I |
| V/E | 0.9454 | likely_pathogenic | 0.9314 | pathogenic | -1.067 | Destabilizing | 0.983 | D | 0.817 | deleterious | N | 0.488426764 | None | None | I |
| V/F | 0.7488 | likely_pathogenic | 0.7298 | pathogenic | -1.187 | Destabilizing | 0.923 | D | 0.757 | deleterious | None | None | None | None | I |
| V/G | 0.8572 | likely_pathogenic | 0.8312 | pathogenic | -1.681 | Destabilizing | 0.949 | D | 0.831 | deleterious | N | 0.49952958 | None | None | I |
| V/H | 0.9862 | likely_pathogenic | 0.9803 | pathogenic | -1.172 | Destabilizing | 0.996 | D | 0.809 | deleterious | None | None | None | None | I |
| V/I | 0.0732 | likely_benign | 0.0672 | benign | -0.713 | Destabilizing | 0.005 | N | 0.219 | neutral | None | None | None | None | I |
| V/K | 0.964 | likely_pathogenic | 0.9539 | pathogenic | -1.109 | Destabilizing | 0.961 | D | 0.819 | deleterious | None | None | None | None | I |
| V/L | 0.3951 | ambiguous | 0.289 | benign | -0.713 | Destabilizing | 0.075 | N | 0.423 | neutral | N | 0.481520711 | None | None | I |
| V/M | 0.4931 | ambiguous | 0.4105 | ambiguous | -0.575 | Destabilizing | 0.901 | D | 0.652 | neutral | N | 0.492021161 | None | None | I |
| V/N | 0.9282 | likely_pathogenic | 0.9041 | pathogenic | -0.893 | Destabilizing | 0.987 | D | 0.839 | deleterious | None | None | None | None | I |
| V/P | 0.7663 | likely_pathogenic | 0.7187 | pathogenic | -0.903 | Destabilizing | 0.987 | D | 0.813 | deleterious | None | None | None | None | I |
| V/Q | 0.9613 | likely_pathogenic | 0.9457 | pathogenic | -1.095 | Destabilizing | 0.987 | D | 0.805 | deleterious | None | None | None | None | I |
| V/R | 0.9566 | likely_pathogenic | 0.9446 | pathogenic | -0.57 | Destabilizing | 0.987 | D | 0.842 | deleterious | None | None | None | None | I |
| V/S | 0.9185 | likely_pathogenic | 0.8882 | pathogenic | -1.443 | Destabilizing | 0.961 | D | 0.797 | deleterious | None | None | None | None | I |
| V/T | 0.8284 | likely_pathogenic | 0.7625 | pathogenic | -1.352 | Destabilizing | 0.775 | D | 0.716 | prob.delet. | None | None | None | None | I |
| V/W | 0.9883 | likely_pathogenic | 0.9859 | pathogenic | -1.301 | Destabilizing | 0.996 | D | 0.78 | deleterious | None | None | None | None | I |
| V/Y | 0.9559 | likely_pathogenic | 0.944 | pathogenic | -1.019 | Destabilizing | 0.961 | D | 0.735 | prob.delet. | None | None | None | None | I |
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.