Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26040 | 78343;78344;78345 | chr2:178568014;178568013;178568012 | chr2:179432741;179432740;179432739 |
| N2AB | 24399 | 73420;73421;73422 | chr2:178568014;178568013;178568012 | chr2:179432741;179432740;179432739 |
| N2A | 23472 | 70639;70640;70641 | chr2:178568014;178568013;178568012 | chr2:179432741;179432740;179432739 |
| N2B | 16975 | 51148;51149;51150 | chr2:178568014;178568013;178568012 | chr2:179432741;179432740;179432739 |
| Novex-1 | 17100 | 51523;51524;51525 | chr2:178568014;178568013;178568012 | chr2:179432741;179432740;179432739 |
| Novex-2 | 17167 | 51724;51725;51726 | chr2:178568014;178568013;178568012 | chr2:179432741;179432740;179432739 |
| 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/F | rs576341346  |
-1.226 | 0.901 | N | 0.639 | 0.215 | 0.628066502817 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 1.79E-05 | 0 |
| V/F | rs576341346 |
-1.226 | 0.901 | N | 0.639 | 0.215 | 0.628066502817 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 2.07383E-04 | 0 |
| V/F | rs576341346 |
-1.226 | 0.901 | N | 0.639 | 0.215 | 0.628066502817 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 1E-03 | None |
| V/F | rs576341346 |
-1.226 | 0.901 | N | 0.639 | 0.215 | 0.628066502817 | gnomAD-4.0.0 | 6.81811E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.90175E-05 | 3.29439E-05 | 3.20205E-05 |
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 | 0.2198 | likely_benign | 0.2588 | benign | -1.467 | Destabilizing | 0.517 | D | 0.501 | neutral | N | 0.40654295 | None | None | N |
| V/C | 0.6789 | likely_pathogenic | 0.7094 | pathogenic | -0.956 | Destabilizing | 0.996 | D | 0.659 | neutral | None | None | None | None | N |
| V/D | 0.7637 | likely_pathogenic | 0.8435 | pathogenic | -1.12 | Destabilizing | 0.983 | D | 0.753 | deleterious | N | 0.478472356 | None | None | N |
| V/E | 0.595 | likely_pathogenic | 0.7094 | pathogenic | -1.022 | Destabilizing | 0.987 | D | 0.704 | prob.neutral | None | None | None | None | N |
| V/F | 0.2992 | likely_benign | 0.341 | ambiguous | -0.916 | Destabilizing | 0.901 | D | 0.639 | neutral | N | 0.486945173 | None | None | N |
| V/G | 0.4386 | ambiguous | 0.5213 | ambiguous | -1.885 | Destabilizing | 0.949 | D | 0.709 | prob.delet. | N | 0.515249282 | None | None | N |
| V/H | 0.8627 | likely_pathogenic | 0.9049 | pathogenic | -1.446 | Destabilizing | 0.996 | D | 0.753 | deleterious | None | None | None | None | N |
| V/I | 0.0667 | likely_benign | 0.0658 | benign | -0.381 | Destabilizing | 0.003 | N | 0.153 | neutral | N | 0.424973995 | None | None | N |
| V/K | 0.8617 | likely_pathogenic | 0.9056 | pathogenic | -1.145 | Destabilizing | 0.961 | D | 0.703 | prob.neutral | None | None | None | None | N |
| V/L | 0.1433 | likely_benign | 0.1665 | benign | -0.381 | Destabilizing | 0.003 | N | 0.18 | neutral | N | 0.382337938 | None | None | N |
| V/M | 0.1453 | likely_benign | 0.1652 | benign | -0.348 | Destabilizing | 0.923 | D | 0.554 | neutral | None | None | None | None | N |
| V/N | 0.5673 | likely_pathogenic | 0.668 | pathogenic | -1.126 | Destabilizing | 0.987 | D | 0.765 | deleterious | None | None | None | None | N |
| V/P | 0.9324 | likely_pathogenic | 0.9499 | pathogenic | -0.709 | Destabilizing | 0.987 | D | 0.726 | prob.delet. | None | None | None | None | N |
| V/Q | 0.6478 | likely_pathogenic | 0.7416 | pathogenic | -1.117 | Destabilizing | 0.987 | D | 0.729 | prob.delet. | None | None | None | None | N |
| V/R | 0.8329 | likely_pathogenic | 0.8803 | pathogenic | -0.853 | Destabilizing | 0.987 | D | 0.761 | deleterious | None | None | None | None | N |
| V/S | 0.3904 | ambiguous | 0.4648 | ambiguous | -1.758 | Destabilizing | 0.961 | D | 0.664 | neutral | None | None | None | None | N |
| V/T | 0.3307 | likely_benign | 0.3863 | ambiguous | -1.524 | Destabilizing | 0.775 | D | 0.469 | neutral | None | None | None | None | N |
| V/W | 0.9126 | likely_pathogenic | 0.9305 | pathogenic | -1.227 | Destabilizing | 0.996 | D | 0.748 | deleterious | None | None | None | None | N |
| V/Y | 0.7346 | likely_pathogenic | 0.7789 | pathogenic | -0.854 | Destabilizing | 0.961 | D | 0.662 | neutral | 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.