Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 33110 | 99553;99554;99555 | chr2:178537879;178537878;178537877 | chr2:179402606;179402605;179402604 |
| N2AB | 31469 | 94630;94631;94632 | chr2:178537879;178537878;178537877 | chr2:179402606;179402605;179402604 |
| N2A | 30542 | 91849;91850;91851 | chr2:178537879;178537878;178537877 | chr2:179402606;179402605;179402604 |
| N2B | 24045 | 72358;72359;72360 | chr2:178537879;178537878;178537877 | chr2:179402606;179402605;179402604 |
| Novex-1 | 24170 | 72733;72734;72735 | chr2:178537879;178537878;178537877 | chr2:179402606;179402605;179402604 |
| Novex-2 | 24237 | 72934;72935;72936 | chr2:178537879;178537878;178537877 | chr2:179402606;179402605;179402604 |
| 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/I | rs765303215  |
-0.53 | 0.006 | N | 0.316 | 0.149 | 0.342168650903 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.59E-05 | None | 0 | None | 0 | 0 | 0 |
| V/I | rs765303215 |
-0.53 | 0.006 | N | 0.316 | 0.149 | 0.342168650903 | gnomAD-4.0.0 | 1.59338E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.775E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.1876 | likely_benign | 0.1767 | benign | -1.19 | Destabilizing | 0.727 | D | 0.49 | neutral | D | 0.527040436 | None | None | N |
| V/C | 0.7094 | likely_pathogenic | 0.7423 | pathogenic | -0.842 | Destabilizing | 0.999 | D | 0.564 | neutral | None | None | None | None | N |
| V/D | 0.4657 | ambiguous | 0.4235 | ambiguous | -0.736 | Destabilizing | 0.991 | D | 0.695 | prob.neutral | D | 0.537774866 | None | None | N |
| V/E | 0.3721 | ambiguous | 0.3341 | benign | -0.782 | Destabilizing | 0.96 | D | 0.617 | neutral | None | None | None | None | N |
| V/F | 0.2418 | likely_benign | 0.2212 | benign | -1.083 | Destabilizing | 0.988 | D | 0.586 | neutral | N | 0.497260715 | None | None | N |
| V/G | 0.3308 | likely_benign | 0.3055 | benign | -1.451 | Destabilizing | 0.977 | D | 0.669 | neutral | D | 0.537014397 | None | None | N |
| V/H | 0.6494 | likely_pathogenic | 0.6536 | pathogenic | -1.05 | Destabilizing | 0.999 | D | 0.709 | prob.delet. | None | None | None | None | N |
| V/I | 0.0778 | likely_benign | 0.0767 | benign | -0.6 | Destabilizing | 0.006 | N | 0.316 | neutral | N | 0.463317031 | None | None | N |
| V/K | 0.4216 | ambiguous | 0.4056 | ambiguous | -0.905 | Destabilizing | 0.981 | D | 0.621 | neutral | None | None | None | None | N |
| V/L | 0.2441 | likely_benign | 0.2427 | benign | -0.6 | Destabilizing | 0.293 | N | 0.501 | neutral | N | 0.461084803 | None | None | N |
| V/M | 0.1338 | likely_benign | 0.1314 | benign | -0.449 | Destabilizing | 0.988 | D | 0.452 | neutral | None | None | None | None | N |
| V/N | 0.3194 | likely_benign | 0.3138 | benign | -0.613 | Destabilizing | 0.886 | D | 0.694 | prob.neutral | None | None | None | None | N |
| V/P | 0.9618 | likely_pathogenic | 0.9539 | pathogenic | -0.761 | Destabilizing | 0.94 | D | 0.672 | neutral | None | None | None | None | N |
| V/Q | 0.3715 | ambiguous | 0.3735 | ambiguous | -0.824 | Destabilizing | 0.987 | D | 0.673 | neutral | None | None | None | None | N |
| V/R | 0.4059 | ambiguous | 0.3809 | ambiguous | -0.429 | Destabilizing | 0.996 | D | 0.72 | prob.delet. | None | None | None | None | N |
| V/S | 0.2489 | likely_benign | 0.2412 | benign | -1.129 | Destabilizing | 0.607 | D | 0.432 | neutral | None | None | None | None | N |
| V/T | 0.1465 | likely_benign | 0.1521 | benign | -1.067 | Destabilizing | 0.085 | N | 0.313 | neutral | None | None | None | None | N |
| V/W | 0.9065 | likely_pathogenic | 0.8966 | pathogenic | -1.206 | Destabilizing | 1.0 | D | 0.729 | prob.delet. | None | None | None | None | N |
| V/Y | 0.6513 | likely_pathogenic | 0.6383 | pathogenic | -0.907 | Destabilizing | 0.999 | D | 0.588 | 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.