Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28918 | 86977;86978;86979 | chr2:178559380;178559379;178559378 | chr2:179424107;179424106;179424105 |
| N2AB | 27277 | 82054;82055;82056 | chr2:178559380;178559379;178559378 | chr2:179424107;179424106;179424105 |
| N2A | 26350 | 79273;79274;79275 | chr2:178559380;178559379;178559378 | chr2:179424107;179424106;179424105 |
| N2B | 19853 | 59782;59783;59784 | chr2:178559380;178559379;178559378 | chr2:179424107;179424106;179424105 |
| Novex-1 | 19978 | 60157;60158;60159 | chr2:178559380;178559379;178559378 | chr2:179424107;179424106;179424105 |
| Novex-2 | 20045 | 60358;60359;60360 | chr2:178559380;178559379;178559378 | chr2:179424107;179424106;179424105 |
| 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/S | None | None | 1.0 | N | 0.738 | 0.604 | 0.484256599201 | gnomAD-4.0.0 | 2.05295E-06 | None | None | None | None | N | None | 2.989E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.7992E-06 | 0 | 0 |
| R/T | None | None | 1.0 | N | 0.747 | 0.53 | 0.762953578078 | gnomAD-4.0.0 | 1.59192E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.88246E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.9551 | likely_pathogenic | 0.9574 | pathogenic | -1.69 | Destabilizing | 1.0 | D | 0.643 | neutral | None | None | None | None | N |
| R/C | 0.4899 | ambiguous | 0.4924 | ambiguous | -1.663 | Destabilizing | 1.0 | D | 0.813 | deleterious | None | None | None | None | N |
| R/D | 0.9967 | likely_pathogenic | 0.9971 | pathogenic | -0.777 | Destabilizing | 1.0 | D | 0.802 | deleterious | None | None | None | None | N |
| R/E | 0.9516 | likely_pathogenic | 0.9527 | pathogenic | -0.574 | Destabilizing | 0.999 | D | 0.673 | neutral | None | None | None | None | N |
| R/F | 0.9811 | likely_pathogenic | 0.9831 | pathogenic | -0.944 | Destabilizing | 1.0 | D | 0.842 | deleterious | None | None | None | None | N |
| R/G | 0.9465 | likely_pathogenic | 0.9509 | pathogenic | -2.037 | Highly Destabilizing | 1.0 | D | 0.742 | deleterious | D | 0.540323673 | None | None | N |
| R/H | 0.3958 | ambiguous | 0.4293 | ambiguous | -1.94 | Destabilizing | 1.0 | D | 0.807 | deleterious | None | None | None | None | N |
| R/I | 0.9236 | likely_pathogenic | 0.9315 | pathogenic | -0.695 | Destabilizing | 1.0 | D | 0.83 | deleterious | N | 0.508229767 | None | None | N |
| R/K | 0.3649 | ambiguous | 0.3523 | ambiguous | -1.288 | Destabilizing | 0.995 | D | 0.659 | neutral | N | 0.48388086 | None | None | N |
| R/L | 0.8691 | likely_pathogenic | 0.8744 | pathogenic | -0.695 | Destabilizing | 1.0 | D | 0.742 | deleterious | None | None | None | None | N |
| R/M | 0.9163 | likely_pathogenic | 0.9214 | pathogenic | -1.195 | Destabilizing | 1.0 | D | 0.807 | deleterious | None | None | None | None | N |
| R/N | 0.9822 | likely_pathogenic | 0.9868 | pathogenic | -1.158 | Destabilizing | 1.0 | D | 0.773 | deleterious | None | None | None | None | N |
| R/P | 0.9993 | likely_pathogenic | 0.9993 | pathogenic | -1.014 | Destabilizing | 1.0 | D | 0.811 | deleterious | None | None | None | None | N |
| R/Q | 0.3281 | likely_benign | 0.3354 | benign | -1.045 | Destabilizing | 1.0 | D | 0.776 | deleterious | None | None | None | None | N |
| R/S | 0.9637 | likely_pathogenic | 0.9698 | pathogenic | -2.008 | Highly Destabilizing | 1.0 | D | 0.738 | prob.delet. | N | 0.510530263 | None | None | N |
| R/T | 0.9406 | likely_pathogenic | 0.9517 | pathogenic | -1.6 | Destabilizing | 1.0 | D | 0.747 | deleterious | N | 0.491046883 | None | None | N |
| R/V | 0.9361 | likely_pathogenic | 0.9437 | pathogenic | -1.014 | Destabilizing | 1.0 | D | 0.804 | deleterious | None | None | None | None | N |
| R/W | 0.8005 | likely_pathogenic | 0.8077 | pathogenic | -0.502 | Destabilizing | 1.0 | D | 0.794 | deleterious | None | None | None | None | N |
| R/Y | 0.9479 | likely_pathogenic | 0.9506 | pathogenic | -0.321 | Destabilizing | 1.0 | D | 0.837 | deleterious | 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.