Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 5571 | 16936;16937;16938 | chr2:178732258;178732257;178732256 | chr2:179596985;179596984;179596983 |
| N2AB | 5254 | 15985;15986;15987 | chr2:178732258;178732257;178732256 | chr2:179596985;179596984;179596983 |
| N2A | 4327 | 13204;13205;13206 | chr2:178732258;178732257;178732256 | chr2:179596985;179596984;179596983 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/S | rs566415754  |
-0.191 | 1.0 | D | 0.665 | 0.586 | 0.607079148747 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| P/S | rs566415754 |
-0.191 | 1.0 | D | 0.665 | 0.586 | 0.607079148747 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.07383E-04 | 0 |
| P/S | rs566415754 |
-0.191 | 1.0 | D | 0.665 | 0.586 | 0.607079148747 | 1000 genomes | 1.99681E-04 | None | None | None | None | I | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 1E-03 | None |
| P/S | rs566415754 |
-0.191 | 1.0 | D | 0.665 | 0.586 | 0.607079148747 | gnomAD-4.0.0 | 6.56918E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.07555E-04 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.1715 | likely_benign | 0.1223 | benign | -0.388 | Destabilizing | 1.0 | D | 0.672 | neutral | D | 0.544997476 | None | None | I |
| P/C | 0.7553 | likely_pathogenic | 0.7443 | pathogenic | -0.753 | Destabilizing | 1.0 | D | 0.665 | neutral | None | None | None | None | I |
| P/D | 0.7336 | likely_pathogenic | 0.6371 | pathogenic | -0.488 | Destabilizing | 1.0 | D | 0.653 | neutral | None | None | None | None | I |
| P/E | 0.5011 | ambiguous | 0.4262 | ambiguous | -0.604 | Destabilizing | 1.0 | D | 0.661 | neutral | None | None | None | None | I |
| P/F | 0.7139 | likely_pathogenic | 0.616 | pathogenic | -0.73 | Destabilizing | 1.0 | D | 0.635 | neutral | None | None | None | None | I |
| P/G | 0.5786 | likely_pathogenic | 0.5279 | ambiguous | -0.467 | Destabilizing | 1.0 | D | 0.641 | neutral | None | None | None | None | I |
| P/H | 0.4318 | ambiguous | 0.3305 | benign | -0.045 | Destabilizing | 1.0 | D | 0.615 | neutral | D | 0.618975536 | None | None | I |
| P/I | 0.4984 | ambiguous | 0.4504 | ambiguous | -0.326 | Destabilizing | 1.0 | D | 0.641 | neutral | None | None | None | None | I |
| P/K | 0.5854 | likely_pathogenic | 0.4706 | ambiguous | -0.477 | Destabilizing | 1.0 | D | 0.657 | neutral | None | None | None | None | I |
| P/L | 0.2048 | likely_benign | 0.1513 | benign | -0.326 | Destabilizing | 1.0 | D | 0.624 | neutral | D | 0.613867913 | None | None | I |
| P/M | 0.4739 | ambiguous | 0.4114 | ambiguous | -0.563 | Destabilizing | 1.0 | D | 0.62 | neutral | None | None | None | None | I |
| P/N | 0.6508 | likely_pathogenic | 0.5377 | ambiguous | -0.261 | Destabilizing | 1.0 | D | 0.628 | neutral | None | None | None | None | I |
| P/Q | 0.3426 | ambiguous | 0.2423 | benign | -0.491 | Destabilizing | 1.0 | D | 0.652 | neutral | None | None | None | None | I |
| P/R | 0.4228 | ambiguous | 0.3085 | benign | 0.015 | Stabilizing | 1.0 | D | 0.625 | neutral | D | 0.634823453 | None | None | I |
| P/S | 0.2809 | likely_benign | 0.1916 | benign | -0.545 | Destabilizing | 1.0 | D | 0.665 | neutral | D | 0.564405178 | None | None | I |
| P/T | 0.2238 | likely_benign | 0.1876 | benign | -0.571 | Destabilizing | 1.0 | D | 0.659 | neutral | D | 0.59976659 | None | None | I |
| P/V | 0.3547 | ambiguous | 0.3069 | benign | -0.317 | Destabilizing | 1.0 | D | 0.622 | neutral | None | None | None | None | I |
| P/W | 0.8443 | likely_pathogenic | 0.7961 | pathogenic | -0.798 | Destabilizing | 1.0 | D | 0.679 | prob.neutral | None | None | None | None | I |
| P/Y | 0.683 | likely_pathogenic | 0.5817 | pathogenic | -0.519 | Destabilizing | 1.0 | D | 0.648 | neutral | 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.